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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. Does the Pittsburgh Severity Score predict outcome in esophageal perforation?

Author: C Wigley, Ewen A. Griffiths, A Athanasiou, Matthew Bedford, A Bhatti, Aziz Sheikh, and James Hodson
Subjects: Male, medicine.medical_specialty, Perforation (oil well), Population, Subgroup analysis, Severity of Illness Index, 03 medical and health sciences, 0302 clinical medicine, Postoperative Complications, Interquartile range, Predictive Value of Tests, Intensive care, Internal medicine, Severity of illness, Medicine, Humans, Hospital Mortality, Prospective Studies, Prospective cohort study, education, Aged, education.field_of_study, Esophageal Perforation, business.industry, Gastroenterology, General Medicine, Length of Stay, Middle Aged, Prognosis, Patient Outcome Assessment, 030220 oncology & carcinogenesis, Predictive value of tests, 030211 gastroenterology & hepatology, Female, business
Abstract: Esophageal perforation is an uncommon and challenging surgical emergency associated with high rates of morbidity and mortality. At present, no consensus exists on optimal management of the condition. The Pittsburgh Severity Score (PSS) is a tool intended to stratify perforation severity and guide treatment. However, there is a paucity of literature examining the validity of the score or its application in a UK population. This study aims to validate the PSS and explore its use in stratifying patients with esophageal perforation into distinct subgroups with differential outcomes in an independent UK study population.All patients treated for esophageal perforation at Queen Elizabeth Hospital, Birmingham between September 2003 and October 2017 were included in this study. Cases were identified using a combination of ICD-10 and OPCS informatics search codes and prospective case collection. Data relating to the clinical presentation, diagnosis, management, and outcome of cases were recorded using a preformed data collection form. PSS predictive performance was assessed against five outcomes: rates of post-perforation and post-operative complications, in-hospital mortality, length of intensive care (ICU/HDU) stay, and total length of hospital stay.A total of 87 cases were identified, consisting of 48 (55%) iatrogenic perforations, 24 (28%) cases of spontaneous (Boerhaave's) perforation, and 15 perforations due to other etiologies (17%). Operative management was favored in this series, with 47% of all perforations being treated surgically. Overall in-hospital mortality was 13%, coupled with a median length of hospital stay of 24 days (interquartile range [IQR]: 12-49), of which a median of 2 days was spent in intensive care facilities (IQR: 0-14). A total of 46% of patients developed post-perforation complications, with 59% of the operatively managed cohort developing complications post-operatively.The PSS was not found to be significantly predictive of post-perforation complications (area under the ROC curve [AUROC]: 0.62, p = 0.053) or in-hospital mortality (AUROC: 0.69, p = 0.057) for the cohort as a whole. However, a subgroup analysis found the accuracy of the PSS to vary considerably by etiology, being significantly predictive of post-perforation complications within the subgroup of Boerhaave's perforations (AUROC: 0.86, p = 0.004).In conclusion, we found that the PSS has some utility in stratifying esophageal perforation severity and predicting specific patient outcomes. However, it appears to be of more value when applied to the subgroup of patients with Boerhaave's perforations.
Published: 2018

3. Airway Management: The Less Popular Skill of Bag-mask Ventilation

Author: Bryan Kerner, Jason C. Wigley, Gerald P Rosen, and Omar Viswanath
Subjects: medicine.medical_specialty, Bag mask ventilation, business.industry, medicine.medical_treatment, 010102 general mathematics, 01 natural sciences, Laryngeal Masks, 03 medical and health sciences, 0302 clinical medicine, Anesthesiology and Pain Medicine, medicine, Tidal Volume, Airway management, 030212 general & internal medicine, 0101 mathematics, business, Intensive care medicine, Anesthetics
Published: 2018

4. Right Coronary Artery In-Stent Obstruction After Transcatheter Aortic Valve Implantation (TAVI)

Author: Andres Bacigalupo Landa, Gerald P Rosen, and Jason C. Wigley
Subjects: medicine.medical_specialty, Transcatheter aortic, medicine.medical_treatment, Coronary Artery Disease, Coronary Angiography, Coronary artery disease, Transcatheter Aortic Valve Replacement, Internal medicine, medicine.artery, medicine, Humans, Aged, business.industry, Right coronary artery obstruction, Graft Occlusion, Vascular, Stent, Drug-Eluting Stents, Aortic Valve Stenosis, medicine.disease, Coronary Vessels, Anesthesiology and Pain Medicine, Coronary Occlusion, Right coronary artery, Cardiology, Female, Cardiology and Cardiovascular Medicine, business
Published: 2018

5. Oxidative Stress and Cardiovascular Risk in Type 1 Diabetes Mellitus: Insights From the DCCT/EDIC Study

Author: W.H. Wilson Tang, Paula McGee, John M. Lachin, Daniel Y. Li, Byron Hoogwerf, Stanley L. Hazen, D.M. Nathan, B. Zinman, O. Crofford, S. Genuth, J. Brown‐Friday, J. Crandall, H. Engel, S. Engel, H. Martinez, M. Phillips, M. Reid, H. Shamoon, J. Sheindlin, R. Gubitosi‐Klug, L. Mayer, S. Pendegast, H. Zegarra, D. Miller, L. Singerman, S. Smith‐Brewer, M. Novak, J. Quin, Saul Genuth, M. Palmert, E. Brown, J. McConnell, P. Pugsley, P. Crawford, W. Dahms, N.S. Gregory, M.E. Lackaye, S. Kiss, R. Chan, A. Orlin, M. Rubin, D. Brillon, V. Reppucci, T. Lee, M. Heinemann, S. Chang, B. Levy, L. Jovanovic, M. Richardson, B. Bosco, A. Dwoskin, R. Hanna, S. Barron, R. Campbell, A. Bhan, D. Kruger, J.K. Jones, P.A. Edwards, J.D. Carey, E. Angus, A. Thomas, A. Galprin, M. McLellan, F. Whitehouse, R. Bergenstal, M. Johnson, K. Gunyou, L. Thomas, J. Laechelt, P. Hollander, M. Spencer, D. Kendall, R. Cuddihy, P. Callahan, S. List, J. Gott, N. Rude, B. Olson, M. Franz, G. Castle, R. Birk, J. Nelson, D. Freking, L. Gill, W. Mestrezat, D. Etzwiler, K. Morgan, L.P. Aiello, E. Golden, P. Arrigg, V. Asuquo, R. Beaser, L. Bestourous, J. Cavallerano, R. Cavicchi, O. Ganda, O. Hamdy, R. Kirby, T. Murtha, D Schlossman, S. Shah, G. Sharuk, P. Silva, P. Silver, M. Stockman, J. Sun, E. Weimann, H. Wolpert, L.M. Aiello, A. Jacobson, L. Rand, J. Rosenzwieg, M.E. Larkin, M. Christofi, K. Folino, J. Godine, P. Lou, C. Stevens, E. Anderson, H. Bode, S. Brink, C. Cornish, D. Cros, L. Delahanty, eManbey, C. Haggan, J. Lynch, C. McKitrick, D. Norman, D. Moore, M. Ong, C. Taylor, D. Zimbler, S. Crowell, S. Fritz, K. Hansen, C. Gauthier‐Kelly, F.J. Service, G. Ziegler, A. Barkmeier, L. Schmidt, B. French, R. Woodwick, R. Rizza, W.F. Schwenk, M. Haymond, J. Pach, J. Mortenson, B. Zimmerman, A. Lucas, R. Colligan, L. Luttrell, M. Lopes‐Virella, S. Caulder, C. Pittman, N. Patel, K. Lee, M. Nutaitis, J. Fernandes, K. Hermayer, S. Kwon, A Blevins, J. Parker, J. Colwell, D. Lee, J. Soule, P. Lindsey, M. Bracey, A. Farr, S. Elsing, T. Thompson, J. Selby, T. Lyons, S. Yacoub‐Wasef, M. Szpiech, D. Wood, R. Mayfield, M. Molitch, D. Adelman, S. Colson, L. Jampol, A. Lyon, M. Gill, Z. Strugula, L. Kaminski, R. Mirza, E. Simjanoski, D. Ryan, C. Johnson, A. Wallia, S. Ajroud‐Driss, P. Astelford, N. Leloudes, A. Degillio, B. Schaefer, S. Mudaliar, G Lorenzi, M. Goldbaum, K. Jones, M. Prince, M. Swenson, I. Grant, R. Reed, R. Lyon, O. Kolterman, M. Giotta, T. Clark, G. Friedenberg, W.I. Sivitz, B. Vittetoe, J. Kramer, M. Bayless, R. Zeitler, H. Schrott, N. Olson, L. Snetselaar, R. Hoffman, J. MacIndoe, T. Weingeist, C. Fountain, R. Miller, S. Johnsonbaugh, M. Patronas, M. Carney, S. Mendley, P. Salemi, R. Liss, M. Hebdon, D. Counts, T. Donner, J. Gordon, R. Hemady, A. Kowarski, D. Ostrowski, S. Steidl, B. Jones, W.H. Herman, C.L. Martin, R. Pop‐Busui, D.A. Greene, M.J. Stevens, N. Burkhart, T. Sandford, J. Floyd, J. Bantle, N. Flaherty, J. Terry, D. Koozekanani, S. Montezuma, N. Wimmergren, B. Rogness, M. Mech, T. Strand, J. Olson, L. McKenzie, C. Kwong, F. Goetz, R. Warhol, D. Hainsworth, D. Goldstein, S. Hitt, J. Giangiacomo, D.S Schade, J.L. Canady, M.R. Burge, A. Das, R.B. Avery, L.H. Ketai, J.E. Chapin, M.L. Schluter, J. Rich, C. Johannes, D. Hornbeck, M. Schutta, P.A. Bourne, A. Brucker, S. Braunstein, S. Schwartz, B.J. Maschak‐Carey, L. Baker, T. Orchard, L. Cimino, T. Songer, B. Doft, S. Olson, D. Becker, D. Rubinstein, R.L. Bergren, J. Fruit, R. Hyre, C. Palmer, N. Silvers, L. Lobes, P. Paczan Rath, P.W. Conrad, S. Yalamanchi, J. Wesche, M. Bratkowksi, S. Arslanian, J. Rinkoff, J. Warnicki, D. Curtin, D. Steinberg, G. Vagstad, R. Harris, L. Steranchak, J. Arch, K. Kelly, P. Ostrosaka, M. Guiliani, M. Good, T. Williams, K. Olsen, A. Campbell, C. Shipe, R. Conwit, D. Finegold, M. Zaucha, A. Drash, A. Morrison, J.I. Malone, M.L. Bernal, P.R. Pavan, N. Grove, E.A. Tanaka, D. McMillan, J. Vaccaro‐Kish, L. Babbione, H. Solc, T.J. DeClue, S. Dagogo‐Jack, C. Wigley, H. Ricks, A. Kitabchi, E. Chaum, M.B. Murphy, S. Moser, D. Meyer, A. Iannacone, S. Yoser, M. Bryer‐Ash, S. Schussler, H. Lambeth, P. Raskin, S. Strowig, M. Basco, S. Cercone, A. Barnie, R. Devenyi, M. Mandelcorn, M. Brent, S. Rogers, A. Gordon, N. Bakshi, B. Perkins, L. Tuason, F. Perdikaris, R. Ehrlich, D. Daneman, K. Perlman, S Ferguson, J. Palmer, R. Fahlstrom, I.H. de Boer, J. Kinyoun, L. Van Ottingham, S. Catton, J. Ginsberg, C. McDonald, J. Harth, M. Driscoll, T. Sheidow, J. Mahon, C. Canny, D. Nicolle, P. Colby, J. Dupre, I. Hramiak, N.W. Rodger, M. Jenner, T. Smith, W. Brown, M. May, J. Lipps Hagan, A. Agarwal, T. Adkins, R. Lorenz, S. Feman, L. Survant, N.H. White, L. Levandoski, G. Grand, M. Thomas, D. Joseph, K. Blinder, G. Shah, D. Burgess, I. Boniuk, J. Santiago, W. Tamborlane, P. Gatcomb, K. Stoessel, P. Ramos, K. Fong, P. Ossorio, J. Ahern, L. Meadema‐Mayer, C. Beck, K. Farrell, J Quin, P. Gaston, R. Trail, J. Lachin, J. Backlund, I. Bebu, B. Braffett, L. Diminick, X. Gao, W. Hsu, K. Klumpp, H. Pan, V. Trapani, P. Cleary, P. McGee, W. Sun, S. Villavicencio, K. Anderson, L. Dews, Naji Younes, B. Rutledge, K. Chan, D. Rosenberg, B. Petty, A. Determan, D. Kenny, C. Williams, C. Cowie, C. Siebert, M. Steffes, V. Arends, J. Bucksa, M. Nowicki, B. Chavers, D. O'Leary, J. Polak, A. Harrington, L. Funk, R Crow, B. Gloeb, S. Thomas, C. O'Donnell, E.Z. Soliman, Z.M. Zhang, Y. Li, C. Campbell, L. Keasler, S. Hensley, J. Hu, M. Barr, T. Taylor, R. Prineas, E.L. Feldman, J.W. Albers, P. Low, C. Sommer, K. Nickander, T. Speigelberg, M. Pfiefer, M. Schumer, M. Moran, J. Farquhar, C. Ryan, D. Sandstrom, M. Geckle, E. Cupelli, F. Thoma, B. Burzuk, T. Woodfill, R. Danis, B. Blodi, D. Lawrence, H. Wabers, S. Gangaputra, S. Neill, M. Burger, J. Dingledine, V. Gama, R. Sussman, M. Davis, L. Hubbard, M. Budoff, S. Darabian, P. Rezaeian, N. Wong, M. Fox, R. Oudiz, L Kim, R. Detrano, K. Cruickshanks, D. Dalton, K. Bainbridge, J. Lima, D. Bluemke, E. Turkbey, der Geest, C. Liu, A. Malayeri, A. Jain, C. Miao, H. Chahal, R. Jarboe, V. Monnier, D. Sell, C. Strauch, S. Hazen, A. Pratt, W. Tang, J. Brunzell, J. Purnell, R. Natarajan, F. Miao, L. Zhang, Z. Chen, A. Paterson, A. Boright, S. Bull, L. Sun, S. Scherer, T.J. Lyons, A. Jenkins, R. Klein, G. Virella, A. Jaffa, R. Carter, J. Stoner, W.T. Garvey, D. Lackland, M. Brabham, D. McGee, D. Zheng, R.K. Mayfield, J. Maynard, H. Wessells, A Sarma, R. Dunn, S. Holt, J. Hotaling, C. Kim, Q. Clemens, J. Brown, and K. McVary
Subjects: medicine.medical_specialty, endocrine system diseases, 030209 endocrinology & metabolism, Disease, 030204 cardiovascular system & hematology, Lower risk, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Diabetes mellitus, medicine, Diseases of the circulatory (Cardiovascular) system, Coronary Heart Disease, Glycemic, Original Research, free radical, Inflammation, Type 1 diabetes, biology, business.industry, Paraoxonase, medicine.disease, paraoxonase, 3. Good health, RC666-701, Cohort, diabetes mellitus, biology.protein, Cardiology and Cardiovascular Medicine, business, Oxidant Stress, Oxidative stress, F2Isoprostane, Biomarkers
Abstract: Background Hyperglycemia leading to increased oxidative stress is implicated in the increased risk for the development of macrovascular and microvascular complications in patients with type 1 diabetes mellitus. Methods and Results A random subcohort of 349 participants was selected from the DCCT / EDIC (Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications) cohort. This included 320 controls and 29 cardiovascular disease cases that were augmented with 98 additional known cases to yield a case cohort of 447 participants (320 controls, 127 cases). Biosamples from DCCT baseline, year 1, and closeout of DCCT , and 1 to 2 years post‐ DCCT ( EDIC years 1 and 2) were measured for markers of oxidative stress, including plasma myeloperoxidase, paraoxonase activity, urinary F 2α isoprostanes, and its metabolite, 2,3 dinor‐8 iso prostaglandin F 2α . Following adjustment for glycated hemoblobin and weighting the observations inversely proportional to the sampling selection probabilities, higher paraoxonase activity, reflective of antioxidant activity, and 2,3 dinor‐8 iso prostaglandin F 2α , an oxidative marker, were significantly associated with lower risk of cardiovascular disease (−4.5% risk for 10% higher paraoxonase, P iso prostaglandin F 2α , P =0.0092). In contrast, the oxidative markers myeloperoxidase and F 2α isoprostanes were not significantly associated with cardiovascular disease after adjustment for glycated hemoblobin. There were no significant differences between DCCT intensive and conventional treatment groups in the change in all biomarkers across time segments. Conclusions Heightened antioxidant activity (rather than diminished oxidative stress markers) is associated with lower cardiovascular disease risk in type 1 diabetes mellitus, but these biomarkers did not change over time with intensification of glycemic control. Clinical Trial Registration URL : https://www.clinicaltrials.gov . Unique identifiers: NCT 00360815 and NCT 00360893.
Published: 2018

6. Percutaneous coronary intervention followed by minimally invasive valve surgery compared with median sternotomy coronary artery bypass graft and valve surgery in patients with prior cardiac surgery

Author: Roy F. Williams, Nirat Beohar, Orlando Santana, Jason C. Wigley, Christos G. Mihos, Steve Xydas, Maurice Mawad, and Angelo LaPietra
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, business.industry, medicine.medical_treatment, Percutaneous coronary intervention, Clopidogrel, medicine.disease, Intensive care unit, Surgery, law.invention, Cardiac surgery, Coronary artery disease, surgical procedures, operative, law, Median sternotomy, Internal medicine, Conventional PCI, Cardiology, Cardiopulmonary bypass, Medicine, Original Article, cardiovascular diseases, business, medicine.drug
Abstract: Background: In patients with prior cardiac surgery requiring re-operative coronary and valve surgery, a hybrid approach of percutaneous coronary intervention followed by minimally invasive valve surgery (PCI + MIVS) may be an alternative to the standard median sternotomy coronary artery bypass and valve surgery (CABG + valve). Methods: The outcomes of patients with prior cardiac surgery, presenting with coronary artery and valvular disease, who underwent PCI + MIVS (N=39) were retrospectively compared with those who underwent CABG + valve (N=28) via a repeat median sternotomy, between February 2009 and April 2014. Results: The mean age for the PCI + MIVS versus CABG + valve group was 75±9 and 72±11 years (P=0.54), respectively. The baseline characteristics were similar between groups, with the exception of a greater prevalence of 1-vessel coronary artery disease and clopidogrel or dual antiplatelet therapy at the time of surgery in the PCI + MIVS group, and more 3-vessel coronary artery disease in those undergoing CABG + valve surgery. The PCI + MIVS approach was associated with a decreased aortic cross-clamp (94 vs . 131 minutes, P=0.001) and cardiopulmonary bypass (128 vs . 190 minutes, P vs . 3.8 units, P=0.001), shorter intensive care unit length of stay (41 vs . 71 hours, P vs . 35.7%, P=0.03), re-intubation (2.6% vs . 17.9%, P=0.04), when compared with CABG + valve. The thirty-day and two-year mortality were similar, being 7.7% vs . 7.1% (P=0.66), and 12.8% vs . 10.7% (P=0.55), in the PCI + MIVS vs . CABG + valve group, respectively. Conclusions: Hybrid PCI + MIVS in patients with prior cardiac surgery is associated with shorter operative times and intensive care unit length of stay, less need for intraoperative blood cell transfusions, decreased use of mechanical ventilation, and similar short-term and follow-up survival, when compared with CABG + valve surgery via median sternotomy. Randomized trials and multicenter registries are needed to further evaluate this approach.
Published: 2017

7. Minimising aseptic loosening in extreme bone resections: custom-made tumour endoprostheses with short medullary stems and extra-cortical plates

Author: Scott Evans, Lee Jeys, Guy Morris, C. Wigley, H. Burton, Jonathan Stevenson, S. Ghezelayagh, and Michael Parry
Subjects: Adult, Male, Reoperation, medicine.medical_specialty, Medullary cavity, Adolescent, Bone Neoplasms, Prosthesis Design, 01 natural sciences, Osseointegration, law.invention, Intramedullary rod, 010104 statistics & probability, 03 medical and health sciences, Young Adult, 0302 clinical medicine, law, Bone plate, medicine, Humans, Orthopedics and Sports Medicine, Femur, Humerus, Tibia, 0101 mathematics, Child, Aged, Aged, 80 and over, Salvage Therapy, 030222 orthopedics, business.industry, Middle Aged, Limb Salvage, Surgery, Prosthesis Failure, medicine.anatomical_structure, Female, Implant, business, Bone Plates, Follow-Up Studies
Abstract: Aims Following the resection of an extensive amount of bone in the treatment of a tumour, the residual segment may be insufficient to accept a standard length intramedullary cemented stem. Short-stemmed endoprostheses conceivably have an increased risk of aseptic loosening. Extra-cortical plates have been added to minimise this risk by supplementing fixation. The aim of this study was to investigate the survivorship of short-stemmed endoprostheses and extra-cortical plates. Patients and Methods The study involved 37 patients who underwent limb salvage surgery for a primary neoplasm of bone between 1998 and 2013. Endoprosthetic replacement involved the proximal humerus in nine, the proximal femur in nine, the distal femur in 13 and the proximal tibia in six patients. There were 12 primary (32%) and 25 revision procedures (68%). Implant survivorship was compared with matched controls. The amount of bone that was resected was > 70% of its length and statistically greater than the standard control group at each anatomical site. Results The mean follow-up was seven years (one to 17). The mean length of the stem was 33 mm (20 to 60) in the humerus and 79 mm (34 to 100) in the lower limb. Kaplan-Meier analysis of survival of the implant according to anatomical site confirmed that there was no statistically significant difference between the short-stemmed endoprostheses and the standard stemmed controls at the proximal humeral (p = 0.84), proximal femoral (p = 0.57), distal femoral (p = 0.21) and proximal tibial (p = 0.61) sites. In the short-stemmed group, no implants with extra-cortical plate osseointegration suffered loosening at a mean of 8.5 years (range 2 to 16 years). Three of ten (30%) without osseointegration suffered aseptic loosening at a mean of 7.7 years (range 2 to 11.5 years). Conclusion When extensive resections of bone are required in the surgical management of tumours, and in revision cases, the addition of extra-cortical plates to short medullary stems has shown non-inferiority to standard length medullary stems and minimises aseptic failure. Cite this article: Bone Joint J 2017;99-B:1689–95.
Published: 2017

8. Time-Based or Attempt Based Training Programmes: A Cost Efficiency Study

Author: C. Wigley, Kash Akhtar, Chetan Khatri, Chim Gupte, and Kapil Sugand
Subjects: Cost efficiency, Operations research, business.industry, Training (meteorology), Medicine, Surgery, General Medicine, Time based, business
Published: 2017
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9. The relationship between attendance and academic performance in further education college A/S psychology students

Author: Stephen C. Wigley
Subjects: Further education, Medical education, Adult education, Higher education, business.industry, education, Mathematics education, Attendance, Allowance (money), Academic achievement, Psychology, business, Education
Abstract: This investigation examined the relationship between attendance and examination performance. Psychology students (179) took A/S psychology modules; their results were correlated with their attendance up to the examination date. The data were subjected to a Pearson Product Moment Correlation and a statistically significant result was found. (p =.221∗∗, significant at 0.01). The influence of an Educational Maintenance Allowance (EMA) on attendance and performance was also assessed. Generally it was found that EMA students do attend classes more regularly than non‐EMA students. However, there was little difference between EMA and non‐EMA students' examination performance rates. Serious concerns are raised about the overall effectiveness of EMA as a means of promoting student examination performance.
Published: 2009
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10. 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

11. Assessment of Morale in Further Education Students Studying for A‐level Examinations

Author: Stephen C. Wigley
Subjects: Extraversion and introversion, media_common.quotation_subject, Self-esteem, Neuroticism, humanities, Education, Developmental psychology, Optimism, Psychoticism, medicine, Anxiety, Personality, medicine.symptom, Big Five personality traits, Psychology, media_common
Abstract: This paper reports the results of an empirical study of psychological morale in further education students. Success in A‐level examinations is dependant on a number of factors, not only intellectual ability but also morale and other personality factors. This investigation aimed to assess the influence of these factors in the 16–18 years age range. The sample consisted of 357 A‐level students (156 male and 201 female). Students were asked to complete a number of inventories measuring various dimensions of personality, including morale, self‐esteem, extraversion, neuroticism, psychoticism and state and trait anxiety. Significant and positive correlations of morale with self‐esteem and extraversion were reported. Significant but negative correlations of morale with neuroticism and state and trait anxiety were reported. A factor analysis of the Well‐being Inventory revealed that the most significant factor was student optimism and belief in their future, but this was often moderated by the influence of anxiet...
Published: 2004
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12. 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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13. Environmental justice: a Louisiana case study

Author: Daniel C. Wigley and Kristin Shrader-Frechette
Subjects: Agricultural industry, Environmental issues, Philosophy and religion
Published: 1996

14. Chronically denervated rat schwann cells respond to GGF in vitro

Author: C. Wigley, H. Li, and S.M. Hall
Subjects: Denervation, Receptor expression, Schwann cell, Biology, Schwann cell proliferation, Cell biology, Cellular and Molecular Neuroscience, medicine.anatomical_structure, Nerve growth factor, nervous system, Neurology, Immunology, medicine, Neuregulin, Neuroglia, Neural cell adhesion molecule
Abstract: C-erbB receptor/neuregulin signalling plays a significant role in Schwann cell function. In vivo, Schwann cells up-regulate expression of c-erbB receptors in the first month after injury, but receptor expression is down-regulated with time to levels that are not detectable immunohistochemically. The inability of chronically denervated Schwann cells to respond adequately to signals derived from regenerating axons may be one reason why delayed repair of an injured peripheral nerve frequently fails. We have examined the effects of GGF on denervated Schwann cells in vitro. A modified delayed dissociation technique was used to obtain adult rat Schwann cells from the distal stumps of transected sciatic nerves which had been acutely (7 days) or chronically (2-6 month) denervated. We found that in vitro denervated Schwann cells invariably expressed p75NTR and c-erbB receptors. There was a progressive decrease in total cell yield and the percentage of cells with Schwann cell phenotype (p75NTR and/S-100 or/laminin or /GFAP or/c-erbB positive); proliferation rate; migratory potential; and expression of the cell adhesion molecules N-CAM and N-cadherin, with increasing time of denervation. Addition of GGF2 had a significant stimulatory effect upon Schwann cell proliferation and migration, and an increased proportion of Schwann cells expressed N-CAM and N-cadherin, suggesting that these responses were mediated via GGF/c-erbB signalling. Our results support the view that it may be possible to manipulate chronically denervated Schwann cells so that they become more responsive to signals derived from regrowing axons.
Published: 1998
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15. Environmental justice: A louisiana case study

Author: Kristin Shrader-Frechette and Daniel C. Wigley
Subjects: Environmental justice, History, media_common.quotation_subject, Doctrine, Agricultural and Biological Sciences (miscellaneous), Racism, Injustice, Prima facie, Informed consent, Law, Political science, Environmental Chemistry, Environmental racism, General Environmental Science, media_common, Equity (law)
Abstract: The paper begins with a brief analysis of the concepts of environmental justice and environmental racism and classism. The authors argue that pollution- and environment-related decision-making is prima facie wrong whenever it results in inequitable treatment of individuals on the basis of race or socio-economic status. The essay next surveys the history of the doctrine of free informed consent and argues that the consent of those affected is necessary for ensuring the fairness of decision-making for siting hazardous facilities. The paper also points out that equal opportunity to environmental protection and free informed consent are important rights. Finally, it presents a case study on the proposed uranium enrichment facility near Homer, Louisiana and argues that siting the plant would violate norms of distributive equity and free informed consent. It concludes that siting the facility is a case of environmental injustice and likely an example of environmental racism or classism.
Published: 1996
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16. Different effects of a macrophage cytokine on proliferation in astrocytes and Schwann cells

Author: S, Khan and C, Wigley
Subjects: Monokines, General Neuroscience, Colforsin, Macrophage Inflammatory Proteins, Second Messenger Systems, Rats, Animals, Newborn, Transforming Growth Factor beta, Astrocytes, Cyclic AMP, Animals, Cytokines, Fibroblast Growth Factor 2, Schwann Cells, Rats, Wistar, Chemokine CCL4, Cell Division, Cells, Cultured, Chemokine CCL3
Abstract: The proliferative response in vitro to a novel macrophage inflammatory protein (MIP) 1 alpha has been investigated in astrocytes and Schwann cells. MIP 1 alpha is growth-inhibitory in all cell systems investigated so far and we show here that this cytokine also inhibits the proliferation of astrocytes. This response is seen most clearly when MIP 1 alpha reduces the proliferative response of astrocytes to a potent mitogen. Elevation of intracellular cyclic AMP with forskolin enhances the effects of MIP 1 alpha. In contrast, we show that the proliferation of cultured Schwann cells is stimulated by MIP 1 alpha, and that stimulation is enhanced by simultaneous exposure to forskolin. The possible consequences of these differing responses are discussed in the context of the acute response to injury and potential for regeneration of the peripheral and central nervous systems.
Published: 1994
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17. Restriction fragment length polymorphism (RFLP) analysis provides evidence for a high degree of homology of mitochondrial DNAs from rat hepatomasVersus normal rat livers

Author: W. C. Wigley, Richard A. Nakashima, J. M. Bayouth, and Xin Li
Subjects: Male, Mitochondrial DNA, DNA Mutational Analysis, Molecular Sequence Data, DNA, Mitochondrial, Biochemistry, Genetic recombination, Electron Transport Complex IV, Rats, Sprague-Dawley, chemistry.chemical_compound, Liver Neoplasms, Experimental, Genetics, Animals, Molecular Biology, Ecology, Evolution, Behavior and Systematics, Gene Rearrangement, Recombination, Genetic, mtDNA control region, Base Sequence, biology, NADH dehydrogenase, NADH Dehydrogenase, DNA, Neoplasm, General Medicine, Gene rearrangement, Molecular biology, Rats, Liver, chemistry, Nucleic acid, biology.protein, Restriction fragment length polymorphism, Polymorphism, Restriction Fragment Length, DNA
Abstract: Where differences have been reported between tumor and normal mitochondrial DNA (mtDNA), they have generally involved limited modifications of the genome (Taira et al., Nucleic Acids Res. 11:1635, 1983; Shay and Werbin, Mutat. Res. 186:149, 1987). However, Corral et al. (Nucleic Acids Res. 16:10935, 1988; 17:5191, 1989) observed recombination between cytochrome oxidase subunit I (COI) and NADH dehydrogenase subunit 6 (ND6), two genes normally on opposite sides of the circular mitochondrial genome. In rat hepatoma mtDNA COI and ND6 were reported to be separated by only 230 base pairs (Corral et al., 1988, 1989). We have performed RFLP analysis on mtDNA from normal rat livers and rat hepatomas, using COI and ND6 probes. Additional experiments compared end-labeled DNA fragments produced by EcoRI and HindIII digestion of mtDNA. These studies failed to provide any evidence for genetic recombination in rat hepatoma mtDNA, even in the same cell line used by Corral et al. Rather, they support the conclusion that mtDNA from tumor and normal tissues exhibits a low degree of heterogeneity.
Published: 1992
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18. 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

19. Rectal cancer in young adults: a series of 102 patients at a tertiary care centre in India

Author: Jay Nath, Benjamin Perakath, M. R. B. Keighley, and C. Wigley
Subjects: Adult, Male, medicine.medical_specialty, Adolescent, Colorectal cancer, India, Adenocarcinoma, Young Adult, Age Distribution, Internal medicine, medicine, Rectal Adenocarcinoma, Humans, Stage (cooking), Young adult, Sex Distribution, Pathological, Aged, Retrospective Studies, Gynecology, Aged, 80 and over, Series (stratigraphy), business.industry, Rectal Neoplasms, Incidence, Gastroenterology, Middle Aged, medicine.disease, T-stage, Histopathology, Female, business
Abstract: Objective Rectal cancer in young patients is uncommon. There is little information on rectal cancer in young adults in India. The aim of this study was to determine the relative incidence of rectal cancer in young patients in India and identify any differences in histological grade and pathological stage between younger and older cohorts. Method All adult patients presenting at a tertiary colorectal unit with primary rectal adenocarcinoma between September 2003 and August 2007 were included. Patients were divided into two groups: 40 years and younger, and older than 40 years. Details regarding patient demographics, preoperative assessment, management and tumour grade and stage were obtained from a prospectively maintained database. Results One hundred and two of 287 patients (35.5%) were 40 or younger at presentation. Younger patients were more likely to present with less favourable histological features (52.0%vs 20.5% (P
Published: 2008

20. Chronically denervated rat Schwann cells respond to GGF in vitro

Author: H, Li, C, Wigley, and S M, Hall
Subjects: Glia Maturation Factor, Receptor, ErbB-3, Receptor, ErbB-2, Nerve Tissue Proteins, Receptors, Nerve Growth Factor, Receptor, Nerve Growth Factor, Proto-Oncogene Proteins, Animals, Nerve Growth Factors, Rats, Wistar, Neural Cell Adhesion Molecules, Cadherins, Denervation, Immunohistochemistry, Sciatic Nerve, Axons, Coculture Techniques, Growth Inhibitors, Recombinant Proteins, Nerve Regeneration, Rats, ErbB Receptors, Phenotype, Female, Schwann Cells, Cell Division
Abstract: C-erbB receptor/neuregulin signalling plays a significant role in Schwann cell function. In vivo, Schwann cells up-regulate expression of c-erbB receptors in the first month after injury, but receptor expression is down-regulated with time to levels that are not detectable immunohistochemically. The inability of chronically denervated Schwann cells to respond adequately to signals derived from regenerating axons may be one reason why delayed repair of an injured peripheral nerve frequently fails. We have examined the effects of GGF on denervated Schwann cells in vitro. A modified delayed dissociation technique was used to obtain adult rat Schwann cells from the distal stumps of transected sciatic nerves which had been acutely (7 days) or chronically (2-6 month) denervated. We found that in vitro denervated Schwann cells invariably expressed p75NTR and c-erbB receptors. There was a progressive decrease in total cell yield and the percentage of cells with Schwann cell phenotype (p75NTR and/S-100 or/laminin or /GFAP or/c-erbB positive); proliferation rate; migratory potential; and expression of the cell adhesion molecules N-CAM and N-cadherin, with increasing time of denervation. Addition of GGF2 had a significant stimulatory effect upon Schwann cell proliferation and migration, and an increased proportion of Schwann cells expressed N-CAM and N-cadherin, suggesting that these responses were mediated via GGF/c-erbB signalling. Our results support the view that it may be possible to manipulate chronically denervated Schwann cells so that they become more responsive to signals derived from regrowing axons.
Published: 1998

21. The molecular genetics of steroid 5 alpha-reductases

Author: D W, Russell, D M, Berman, J T, Bryant, K M, Cala, D L, Davis, C P, Landrum, J S, Prihoda, R I, Silver, A E, Thigpen, and W C, Wigley
Subjects: Isoenzymes, 3-Oxo-5-alpha-Steroid 4-Dehydrogenase, Molecular Sequence Data, Mutation, Animals, Humans, Sequence Homology, Amino Acid Sequence
Published: 1994

22. Advances in technology of bulk starter production and cheesemaking

Author: R. C. Wigley
Subjects: Engineering, Starter, Work (electrical), Waste management, business.industry, Process Chemistry and Technology, Production (economics), Bioengineering, Cheesemaking, business, Food Science, Biotechnology
Abstract: The paper describes the author's proposals for a bulk starter preparation facility for a cheese creamery handling 500,000 litres of milk per day. The use of Direct Vat Inoculation (DVI) is discussed and work with various systems is reviewed.
Published: 1980
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23. Interferon gamma regulates accumulation of the proteasome activator PA28 and immunoproteasomes at nuclear PML bodies.

Author: P, Fabunmi R, C, Wigley W, J, Thomas P, and N, DeMartino G
Abstract: PA28 is an interferon (gamma) (IFN(gamma)) inducible proteasome activator required for presentation of certain major histocompatibility (MHC) class I antigens. Under basal conditions in HeLa and Hep2 cells, a portion of nuclear PA28 is concentrated at promyelocytic leukemia oncoprotein (PML)-containing bodies also commonly known as PODs or ND10. IFN(gamma) treatment greatly increased the number and size of the PA28- and PML-containing bodies, and the effect was further enhanced in serum-deprived cells. PML bodies are disrupted in response to certain viral infections and in diseases such as acute promyelocytic leukemia (APL). Like PML, PA28 was delocalized from PML bodies by expression of the cytomegalovirus protein, IE1, and in NB4 cells, an APL model line. Moreover, retinoic acid treatment, which causes remission of APL in patients and reformation of PML-containing bodies in NB4 cells, relocalized PA28 to this site. In contrast, the proteasome, the functional target of PA28, was not detected at PML bodies under basal conditions in HeLa and Hep2 cells, but IFN(gamma) promoted accumulation of 'immunoproteasomes' at this site. These results establish PA28 as a novel component of nuclear PML bodies, and suggest that PA28 may assemble or activate immunoproteasomes at this site as part of its role in proteasome-dependent MHC class I antigen presentation.
Published: 2001

24. ACTIVE INTERVENTION IN THE TREATMENT OF PULMONARY TUBERCULOSIS

Author: S. C. Wigley
Subjects: medicine.medical_specialty, Tuberculosis, Pulmonary tuberculosis, business.industry, Internal medicine, Intervention (counseling), medicine, General Medicine, medicine.disease, business
Published: 1955
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25. BCG vaccination in leprosy: final results of the trial in Karimui, Papua New Guinea, 1963-79

Author: A, Bagshawe, G C, Scott, D A, Russell, S C, Wigley, A, Merianos, and G, Berry
Subjects: Male, Clinical Trials as Topic, Adolescent, Incidence, Infant, Newborn, Infant, complex mixtures, Papua New Guinea, Random Allocation, Child, Preschool, Leprosy, BCG Vaccine, Prevalence, Humans, Female, Child, Research Article
Abstract: The efficacy of BCG vaccine in preventing the clinical manifestations of leprosy in a tuberculosis-free area of Papua New Guinea is reported. Between 1963 and 1966 a total of 5356 subjects, randomized to receive BCG or saline inoculations, were examined for leprosy before the vaccination and surveillance was continued until 1979. BCG afforded 48% protection against clinical leprosy, being most effective against borderline tuberculoid leprosy and in children vaccinated when under 15 years old. Protection was evident within 12 months in those vaccinated between the ages of 10 and 15 years but was delayed in other age groups. There was evidence for accelerated manifestations of tuberculoid leprosy in children vaccinated when under 5 years of age. Tuberculin sensitivity was more likely to be sustained following multiple BCG inoculations; vaccinees with sustained tuberculin sensitivity had the lowest incidence of leprosy, but protection was also evident in tuberculin-negative vaccinees. These results may have implications for ongoing trials of leprosy vaccine incorporating BCG.
Published: 1989

26. Polyserositis and pericarditis in Melanesians with considerations on the evolution of tuberculous infection in man

Author: S C, Wigley
Subjects: Adult, Male, Serositis, Adolescent, Pericarditis, Constrictive, Humans, Female, Melanesia, Pericarditis, Tuberculous, Tuberculosis, Cardiovascular, Tuberculosis, Pulmonary
Published: 1974

27. Defaulter and abscondee: a Melanesian miscellany

Author: K, Wari and S C, Wigley
Subjects: New Guinea, Patient Dropouts, Culture, Allied Health Personnel, Ambulatory Care, Humans, Tuberculosis, Medicine, Traditional, Magic
Published: 1974

28. Post-vaccination (BCG) conversion reactions in a tuberculosis-free community

Author: S C, Wigley
Subjects: Mycobacterium Infections, New Guinea, Time Factors, Tuberculin Test, BCG Vaccine, Humans, Child, School Health Services
Published: 1974

29. BCG in Papua--New Guinea

Author: S C, Wigley
Subjects: New Guinea, Adolescent, Tuberculin Test, BCG Vaccine, Infant, Newborn, Humans, Tuberculosis, Child
Published: 1974

30. Psychosomatics of tuberculosis

Author: S C, Wigley
Subjects: Life Change Events, Stress, Physiological, Adaptation, Psychological, Humans, Tuberculosis, Melanesia, Psychophysiologic Disorders, Stress, Psychological
Published: 1980

31. Lung cancer and the Melanesian. An impending problem?

Author: S C, Wigley
Subjects: Adult, Male, New Guinea, Lung Neoplasms, Sex Factors, Geography, Age Factors, Humans, Female, Middle Aged, Lung, Aged
Published: 1974

32. Pulmonary infection in Sjögren's disease (keratoconjunctivitis sicca): a report of a fatal case

Author: S C, WIGLEY and J B, EGAN
Subjects: Lung Diseases, Sjogren's Syndrome, Keratoconjunctivitis, Humans, Keratoconjunctivitis Sicca, Respiratory Tract Infections
Published: 1955

33. BCG VACCINATION IN LEPROSY. A PRELIMINARY REPORT OF A 'BLIND' CONTROLLED TRIAL

Author: D A, RUSSELL, G C, SCOTT, and S C, WIGLEY
Subjects: New Guinea, Epidemiology, Leprosy, Vaccination, BCG Vaccine, Humans, Mycobacterium bovis, Visually Impaired Persons, Ethnology
Published: 1964

34. THE COLLECTED PAPERS OF SIR THOMAS HAVELOCK ON HYDRODYNAMICS

Author: C. Wigley
Subjects: Naval architecture, Physics, Classical mechanics, Drag, Fluid dynamics, Wake, Motion (physics)
Published: 1965
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35. Analysis of the forces and moments on a yawing ship

Author: C. Wigley
Subjects: Scale effect, Mathematics, Marine engineering
Abstract: In view of the increase in the number of Steering Tanks, it appears that an analysis of the forces and moments on a ship when yawing or turning is needed, in particular to determine the scale effect between model and ship.
Published: 1966
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36. Do frailty scores predict outcome after proximal femoral replacement for musculoskeletal tumours: a case series?

Author: Buldu MT, Wigley C, Kapoor S, Bassett P, and Gerrand C
Subjects: Humans, Aged, Middle Aged, Frail Elderly, Retrospective Studies, Quality of Life, Postoperative Complications epidemiology, Risk Factors, Frailty complications, Frailty diagnosis, Frailty epidemiology, Neoplasms
Abstract: Purpose: Frailty has a negative independent relationship with morbidity and mortality. A frail individual has low resilience and adaptive capacity to stressors with unfavourable consequences. The relationship between musculoskeletal tumour patients undergoing surgery and frailty is underrepresented in literature. This study's questions are; what is the prevalence of frailty in patients undergoing surgery for musculoskeletal tumours; what is the correlation between frailty and survival plus secondary outcome measures including length of hospital stay (LOS); can clinicians use frailty scoring to support preoperative decision-making?, Methods: Patients over 60 years of age undergoing proximal femoral replacement for musculoskeletal tumours were included and classified as fit, vulnerable or frail using the modified frailty index (mFI), Rockwood and American Society of Anaesthesiologist's physical status classification (ASA) grading systems. Correlation with outcomes including survival and (LOS) was determined., Results: 85 patients were identified of mean age 72.6 years. Median follow-up was 18.9 months. The prevalence of frailty ranged between 55 to 76% and the overall median survival in frail groups were 19.8 months with all scoring systems used. Frail patients classified by the Rockwood score had a greater LOS and a trend to reduced survival., Conclusions: There is a high prevalence of frailty in this cohort and frailty scores should be considered when planning surgery as part of holistic care. Moreover, a median survival greater than 18 months in frail patients supports the decision to offer surgery which may positively impact quality of life. Further research to identify the relationship between frailty and outcomes in musculoskeletal tumour patients is needed., Level of Evidence: IV, Retrospective Case Series., (© 2021. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)
Published: 2023
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37. Re: Best et al., 'Unlocking the potential of the UK 100,000 Genomes Project - Lessons learned from analysis of the "Congenital malformations caused by ciliopathies" cohort'.

Author: Brown MA, Wigley C, Walker S, Lancaster D, Rendon A, and Scott R
Subjects: Cohort Studies, Humans, United Kingdom epidemiology, Ciliopathies
Published: 2022
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38. Developing a National Newborn Genomes Program: An Approach Driven by Ethics, Engagement and Co-design.

Author: Pichini A, Ahmed A, Patch C, Bick D, Leblond M, Kasperaviciute D, Deen D, Wilde S, Garcia Noriega S, Matoko C, Tuff-Lacey A, Wigley C, and Scott RH
Abstract: The transformative potential of whole genome sequencing (WGS) as a diagnostic tool in healthcare has been demonstrated by initiatives including the 100,000 Genomes Project and is now offered to certain patients in the National Health Service (NHS) in England. Building on these foundations, the utility of WGS in the newborn period can now be explored. Genomics England is working in partnership with NHS England and NHS Improvement and other healthcare, patient and public interest groups to design a research program embedded in the NHS to explore the potential challenges and implications of offering WGS in all newborns. The program will aim to: 1) evaluate the feasibility, utility and impact on the NHS of screening for childhood-onset rare actionable genetic conditions; 2) understand how, with consent, genomic and healthcare data could be used to enable research to develop new diagnostics and treatments; and 3) explore the implications of storing an individual's genome for use over their lifetime. Recognizing the important practical, scientific and ethical questions that we must explore in dialogue with the public and experts, we are taking a collaborative, evidence-based and ethically deliberate approach to designing the program. An iterative co-design process including a nationwide public dialogue has identified emergent themes and ethical considerations which are the focus of the program's design. These themes will be further developed through continued engagement with healthcare professionals, researchers, ethics experts, patient groups and the public, with an ongoing commitment to embedding ongoing ethics research and co-design into the delivery of the program., Competing Interests: AP, AA, DB, ML, DK, DD, SW, SG, SM, AT-L, CW, and RS are all employed by Genomics England. CP was employed by Genomics England until December 2021., (Copyright © 2022 Pichini, Ahmed, Patch, Bick, Leblond, Kasperaviciute, Deen, Wilde, Garcia Noriega, Matoko, Tuff-Lacey, Wigley and Scott.)
Published: 2022
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39. Ectopic extramammary Paget's disease of the abdominal wall with abdominoplasty reconstruction.

Author: Wigley C, Zargaran D, Nikkhah D, and Butler P
Subjects: Female, Humans, Middle Aged, Abdominal Wall pathology, Abdominal Wall surgery, Abdominoplasty, Paget Disease, Extramammary pathology, Paget Disease, Extramammary surgery, Transplants pathology
Abstract: Ectopic extramammary Paget's disease describes an exceedingly rare intraepithelial adenocarcinoma arising within non-apocrine tissues. We present a case report of E-EPMD arising on the lower abdomen without underlying secondary malignancy in a 56-year-old female patient. We performed a wide local excision of the lesion with subsequent mini abdominoplasty reconstruction., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)
Published: 2022
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40. Pelvic Ewing sarcoma: Should all patients receive pre-operative radiotherapy, or should it be delivered selectively?

Author: Lex JR, Kurisunkal V, Kaneuchi Y, Fujiwara T, Sherriff J, Wigley C, Stevenson JD, Parry MC, and Jeys LM
Subjects: Adolescent, Adult, Bone Neoplasms pathology, Child, Female, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Necrosis, Neoadjuvant Therapy, Neoplasm Metastasis, Pelvic Bones, Preoperative Period, Proton Therapy adverse effects, Radiotherapy, Adjuvant, Retrospective Studies, Sarcoma, Ewing secondary, Surgical Wound Infection etiology, Survival Rate, Tumor Burden, Young Adult, Bone Neoplasms radiotherapy, Bone Neoplasms surgery, Neoplasm Recurrence, Local pathology, Sarcoma, Ewing radiotherapy, Sarcoma, Ewing surgery
Abstract: Background: Locally recurrent disease following surgical resection of Ewing sarcoma (ES) confers a poor prognosis. Limited evidence is available evaluating non-selective use of pre-operative radiotherapy (RT) for patients with pelvic ES and its effect on local control and survival., Patients and Methods: 49 consecutive patients with pelvic ES were identified retrospectively from a prospectively collated database. Patients either received non-selective pre-operative RT and surgery (n = 27), or selective post-operative RT (n = 22) (surgery alone (n = 11) or surgery and post-operative RT (n = 11))., Results: Patients who had non-selective pre-operative radiotherapy appeared to have a higher LRFS, 88.0% compared to 66.5% in the selective RT group (p = 0.096, Kaplan Meier; p = 0.028, Chi-squared). Administration of non-selective, pre-operative RT to all patients with pelvic ES elevates the LFRS to that of the good responder group (≥90% tumour necrosis and margins, p = 0.880). There was no difference in metastasis-free survival, 60.0% and 54.5% (p = 0.728) and overall survival (OS), 57.7% and 63.6% (p = 0.893). The majority of pre-operative RT patients had both good necrosis (≥90%) (p = 0.003) and widely excised tumours, 81.5% vs 59.1% (p = 0.080). Tumour volume ≥250 ml was associated with worse LRFS (p = 0.045) and post-operative complications (p = 0.017). There may be improved LRFS (p = 0.057) with pre-operative proton-beam RT compared to surgery and selective post-operative RT., Conclusion: Pre-operative photon or proton-beam RT to all pelvic ES may improve LRFS compared to the selective delivery of post-operative RT. Radiotherapy delivered to all patients results in a greater percentage of highly necrotic tumours at surgical excision, enabling a greater proportion of patients with wide resection margins., Competing Interests: Declaration of competing interest Each author certifies that he or she has no commercial associations (e.g. Consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article., (Crown Copyright © 2021. Published by Elsevier Ltd. All rights reserved.)
Published: 2021
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41. Extra-abdominal desmoid tumor fibromatosis: a multicenter EMSOS study.

Author: Cuomo P, Scoccianti G, Schiavo A, Tortolini V, Wigley C, Muratori F, Matera D, Kukushkina M, Funovics PT, Lingitz MT, Windhager R, Dijkstra S, Jasper J, Müller DA, Kaiser D, Perlaky T, Leithner A, Smolle MA, and Campanacci DA
Subjects: Adolescent, Adult, Aged, Aged, 80 and over, Biopsy, Child, Child, Preschool, Combined Modality Therapy, Disease Management, Disease Progression, Female, Fibromatosis, Abdominal diagnosis, Fibromatosis, Aggressive diagnosis, Humans, Male, Middle Aged, Prognosis, Recurrence, Retrospective Studies, Treatment Outcome, Young Adult, Fibromatosis, Abdominal mortality, Fibromatosis, Abdominal therapy, Fibromatosis, Aggressive mortality, Fibromatosis, Aggressive therapy
Abstract: Background: Extra-abdominal desmoid tumor fibromatosis (DTF) is a rare, locally aggressive soft tissue tumour. The best treatment modality for this patient cohort is still object of debate., Questions/purpose: This paper aimed to (1) to compare the outcomes of DTF after different treatment modalities, (2) to assess prognostic factors for recurrence following surgical excision, and (3) to assess prognostic factors for progression during observation., Methods: This was a retrospective multicenter study under the patronage of the European Musculoskeletal Oncology Society (EMSOS). All seven centres involved were tertiary referral centres for soft tissue tumours. Baseline demographic data was collected for all patients as well as data on the diagnosis, tumour characteristics, clinical features, treatment modalities and whether they had any predisposing factors for DTF., Results: Three hundred eighty-eight patients (240 female, 140 male) with a mean age of 37.6 (±18.8 SD, range: 3-85) were included in the study. Two hundred fifty-seven patients (66%) underwent surgical excision of ADF, 70 patients (18%) were observed without therapy, the residual patients had different conservative treatments. There were no significant differences in terms of tumour recurrence or progression between the different treatment groups. After surgical excision, younger age, recurrent disease and larger tumour size were risk factors for recurrence, while tumours around the shoulder girdle and painful lesions were at risk of progression in the observational group., Conclusion: Local recurrence rate after surgery was similar to progression rates under observation. Hence, observation in DTF seems to be justified, considering surgery in case of dimensional progression in 2 consecutive controls (3 and 6 months) and in painful lesions, with particular attention to lesions around the shoulder girdle.
Published: 2021
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42. Response to: 'Concerns about the evidence in relation to implementation of the ProFHER trial' by Handoll et al .

Author: Reeves K, Chan S, Marsh A, Gallier S, Wigley C, Khunti K, and Lilford RJ
Subjects: Orthopedic Procedures, Orthopedics
Abstract: Competing Interests: Competing interests: None declared.
Published: 2020
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43. Implementation of research evidence in orthopaedics: a tale of three trials.

Author: Reeves K, Chan S, Marsh A, Gallier S, Wigley C, Khunti K, and Lilford RJ
Subjects: Ankle Fractures therapy, Health Knowledge, Attitudes, Practice, Humans, Humerus injuries, Radius Fractures therapy, United Kingdom epidemiology, Clinical Trials as Topic, Fractures, Bone therapy, Orthopedic Procedures methods, Orthopedics methods, Practice Patterns, Physicians'
Abstract: Objective: To examine implementation of evidence in orthopaedic practice following publication of the results of three pivotal clinical trials., Design: Case studies based on three orthopaedic trials funded in sequence by the National Institute for Health Research Health Technology Assessment (HTA) programme. These trials dealt with treatment of fractures of the humerus, radius and ankle, respectively. For each case study, we conducted time-series analyses to examine the relationship between publication of findings and the implementation (or not) of the findings., Results: The results of all three trials favoured the less expensive and less invasive option. In two cases, a change of practice, in line with the evidence that eventually emerged, preceded publication. Furthermore, the upturn in use of the intervention most supported by each of these two trials corresponded to the start of recruitment to the respective trial. The remaining trial failed to influence practice despite yielding clear-cut evidence., Conclusions: Implementation of results of all three HTA orthopaedic trials favoured the less expensive and less invasive option. In two of the three studies, a change in practice, in line with the evidence that eventually emerged, preceded publication of that evidence. A trend or a change in practice, at around the start of the trial, indicates that the direction of causation opposes our hypothesis that publication of trial findings would lead to changes in practice. Our results provide provocative insight into the nuanced topic of research and practice, but further qualitative work is needed to fully explain what led to the pre-emptive change in practice we observed and why there was no change in the third case., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)
Published: 2020
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44. Severe drought limits trees in a semi-arid savanna.

Author: Case MF, Wigley-Coetsee C, Nzima N, Scogings PF, and Staver AC
Subjects: Droughts, Ecosystem, Grassland, South Africa, Fires, Trees
Abstract: Increasingly frequent and severe droughts under climate change are expected to have major impacts on vegetation worldwide. However, research to date has focused on tree vulnerability to drought in forests. Less is known about trees and drought in savannas, where a sparse tree layer coexists with grass. These tree-grass interactions (often mediated by fire and herbivory) shape savanna tree ecology, and confound predictions of how strongly drought might affect trees. On the one hand, drought is physiologically stressful, which could harm trees and be exacerbated by herbivore impacts; on the other hand, trees adapted to semiarid savannas might be relatively drought tolerant, and the considerable impacts of drought on grass could even benefit trees via reduced grass competition and fire risk, especially in the year following a drought. Here, we sought to understand the net effects of severe drought on the savanna tree layer, and how fire and herbivory mediate these effects. We monitored tree growth, mortality, and community structure for 2 yr within existing long-term fire and herbivory experiments across a drought-severity contrast, following a major drought in Kruger National Park, South Africa. Overall, severe drought was a major stressor for trees. Tree mortality rates in most species increased by an order of magnitude in the year following drought, and slower growth rates for some persisted for 2 yr. At the community level, this translated into substantial decreases in tree densities. Herbivory and fire did little either to mitigate or exacerbate drought effects on trees, and overall, drought swamped effects of herbivory and fire that have otherwise been observed. However, species differed in their responses to drought, with some dominant encroaching species especially vulnerable. We suggest that increasing drought frequency and severity could drastically alter savanna vegetation by repeatedly killing off trees., (© 2019 by the Ecological Society of America.)
Published: 2019
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45. Does the Pittsburgh Severity Score predict outcome in esophageal perforation?

Author: Wigley C, Athanasiou A, Bhatti A, Sheikh A, Hodson J, Bedford M, and Griffiths EA
Subjects: Aged, Esophageal Perforation mortality, Esophageal Perforation therapy, Female, Hospital Mortality, Humans, Length of Stay statistics & numerical data, Male, Middle Aged, Postoperative Complications etiology, Postoperative Complications mortality, Predictive Value of Tests, Prognosis, Prospective Studies, Esophageal Perforation diagnosis, Patient Outcome Assessment, Severity of Illness Index
Abstract: Esophageal perforation is an uncommon and challenging surgical emergency associated with high rates of morbidity and mortality. At present, no consensus exists on optimal management of the condition. The Pittsburgh Severity Score (PSS) is a tool intended to stratify perforation severity and guide treatment. However, there is a paucity of literature examining the validity of the score or its application in a UK population. This study aims to validate the PSS and explore its use in stratifying patients with esophageal perforation into distinct subgroups with differential outcomes in an independent UK study population.All patients treated for esophageal perforation at Queen Elizabeth Hospital, Birmingham between September 2003 and October 2017 were included in this study. Cases were identified using a combination of ICD-10 and OPCS informatics search codes and prospective case collection. Data relating to the clinical presentation, diagnosis, management, and outcome of cases were recorded using a preformed data collection form. PSS predictive performance was assessed against five outcomes: rates of post-perforation and post-operative complications, in-hospital mortality, length of intensive care (ICU/HDU) stay, and total length of hospital stay.A total of 87 cases were identified, consisting of 48 (55%) iatrogenic perforations, 24 (28%) cases of spontaneous (Boerhaave's) perforation, and 15 perforations due to other etiologies (17%). Operative management was favored in this series, with 47% of all perforations being treated surgically. Overall in-hospital mortality was 13%, coupled with a median length of hospital stay of 24 days (interquartile range [IQR]: 12-49), of which a median of 2 days was spent in intensive care facilities (IQR: 0-14). A total of 46% of patients developed post-perforation complications, with 59% of the operatively managed cohort developing complications post-operatively.The PSS was not found to be significantly predictive of post-perforation complications (area under the ROC curve [AUROC]: 0.62, p = 0.053) or in-hospital mortality (AUROC: 0.69, p = 0.057) for the cohort as a whole. However, a subgroup analysis found the accuracy of the PSS to vary considerably by etiology, being significantly predictive of post-perforation complications within the subgroup of Boerhaave's perforations (AUROC: 0.86, p = 0.004).In conclusion, we found that the PSS has some utility in stratifying esophageal perforation severity and predicting specific patient outcomes. However, it appears to be of more value when applied to the subgroup of patients with Boerhaave's perforations.
Published: 2019
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46. Carnivore stable carbon isotope niches reflect predator-prey size relationships in African savannas.

Author: Codron J, Avenant NL, Wigley-Coetsee C, and Codron D
Subjects: Africa, Animals, Carbon Isotopes, Food Chain, Fossils, Herbivory, Body Size, Carbon chemistry, Carnivora physiology, Grassland, Predatory Behavior
Abstract: Predator-prey size relationships are among the most important patterns underlying the structure and function of ecological communities. Indeed, these relationships have already been shown to be important for understanding patterns of macroevolution and differential extinction in the terrestrial vertebrate fossil record. Stable isotope analysis (SIA) is a powerful remote approach to examining animal diets and paleodiets. The approach is based on the principle that isotope compositions of consumer tissues reflect those of their prey. In systems where resource isotope compositions are distributed along a body size gradient, SIA could be used to reconstruct predator-prey size relationships. We analyzed stable carbon isotope distributions amongst mammalian herbivores in extant and Plio-Pleistocene African savanna assemblages, and show that the range of δ 13 C values among mammalian prey species (herbivores and rodents) increases with body mass (BM), because C 4 plant feeding (essentially grazing) is more common among larger taxa. Consequently, δ 13 C values of mammalian carnivores in these systems are related to species' BM, reflecting a higher average C 4 prey component in the diets of larger-bodied carnivores. This pattern likely emerges because only the largest carnivores in these systems have regular access to the C 4 prey base, whereas smaller carnivores do not. The δ 13 C-BM relationship observed in mammalian carnivores is a potentially powerful approach for reconstructing and parameterizing predator-prey size relationships in contemporary and fossil savanna assemblages, and for interpreting how various behavioral, ecological and environmental factors influence prey size selection., (© 2017 International Society of Zoological Sciences, Institute of Zoology/Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.)
Published: 2018
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47. Santa's little helpers: a novel approach to developing patient information leaflets.

Author: Wigley C, Bucknall V, and Fleming S
Abstract: Competing Interests: Competing interests: We have read BMJ policy on competing interests and declare the following: none.
Published: 2017
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48. Minimising aseptic loosening in extreme bone resections: custom-made tumour endoprostheses with short medullary stems and extra-cortical plates.

Author: Stevenson JD, Wigley C, Burton H, Ghezelayagh S, Morris G, Evans S, Parry M, and Jeys L
Subjects: Adolescent, Adult, Aged, Aged, 80 and over, Bone Plates, Child, Female, Femur surgery, Follow-Up Studies, Humans, Humerus surgery, Limb Salvage methods, Male, Middle Aged, Reoperation, Salvage Therapy instrumentation, Tibia surgery, Young Adult, Bone Neoplasms surgery, Limb Salvage instrumentation, Prosthesis Design, Prosthesis Failure
Abstract: Aims: Following the resection of an extensive amount of bone in the treatment of a tumour, the residual segment may be insufficient to accept a standard length intramedullary cemented stem. Short-stemmed endoprostheses conceivably have an increased risk of aseptic loosening. Extra-cortical plates have been added to minimise this risk by supplementing fixation. The aim of this study was to investigate the survivorship of short-stemmed endoprostheses and extra-cortical plates., Patients and Methods: The study involved 37 patients who underwent limb salvage surgery for a primary neoplasm of bone between 1998 and 2013. Endoprosthetic replacement involved the proximal humerus in nine, the proximal femur in nine, the distal femur in 13 and the proximal tibia in six patients. There were 12 primary (32%) and 25 revision procedures (68%). Implant survivorship was compared with matched controls. The amount of bone that was resected was > 70% of its length and statistically greater than the standard control group at each anatomical site., Results: The mean follow-up was seven years (one to 17). The mean length of the stem was 33 mm (20 to 60) in the humerus and 79 mm (34 to 100) in the lower limb. Kaplan-Meier analysis of survival of the implant according to anatomical site confirmed that there was no statistically significant difference between the short-stemmed endoprostheses and the standard stemmed controls at the proximal humeral (p = 0.84), proximal femoral (p = 0.57), distal femoral (p = 0.21) and proximal tibial (p = 0.61) sites. In the short-stemmed group, no implants with extra-cortical plate osseointegration suffered loosening at a mean of 8.5 years (range 2 to 16 years). Three of ten (30%) without osseointegration suffered aseptic loosening at a mean of 7.7 years (range 2 to 11.5 years)., Conclusion: When extensive resections of bone are required in the surgical management of tumours, and in revision cases, the addition of extra-cortical plates to short medullary stems has shown non-inferiority to standard length medullary stems and minimises aseptic failure. Cite this article: Bone Joint J 2017;99-B:1689-95., (©2017 The British Editorial Society of Bone & Joint Surgery.)
Published: 2017
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49. Motor timing and precursor literacy skills in very young children.

Author: Wigley C, Fletcher J, and Davidson J
Subjects: Awareness, Child, Preschool, Female, Humans, Male, Motor Activity physiology, Pattern Recognition, Visual physiology, Phonetics, Psychomotor Performance physiology, Reading
Abstract: It is generally agreed that efficiency in processing basic speech sounds is a strong indicator of literacy outcomes. However, there is some debate about the extent to which this capacity is encapsulated within the language system. We report results based on pretest data obtained in an early music training study investigating the relationship between a motor-rhythmic measure of ability (synchronous tapping) and the purported purely linguistically based processing measures, Rapid Automatized Naming (RAN) and Phonological Awareness (PA). Results suggest that RAN ability relies to some extent on nonlinguistic temporal processing skills.
Published: 2009
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50. Rectal cancer in young adults: a series of 102 patients at a tertiary care centre in India.

Author: Nath J, Wigley C, Keighley MR, and Perakath B
Subjects: Adenocarcinoma pathology, Adolescent, Adult, Age Distribution, Aged, Aged, 80 and over, Female, Humans, Incidence, India epidemiology, Male, Middle Aged, Rectal Neoplasms pathology, Retrospective Studies, Sex Distribution, Young Adult, Adenocarcinoma epidemiology, Rectal Neoplasms epidemiology
Abstract: Objective: Rectal cancer in young patients is uncommon. There is little information on rectal cancer in young adults in India. The aim of this study was to determine the relative incidence of rectal cancer in young patients in India and identify any differences in histological grade and pathological stage between younger and older cohorts., Method: All adult patients presenting at a tertiary colorectal unit with primary rectal adenocarcinoma between September 2003 and August 2007 were included. Patients were divided into two groups: 40 years and younger, and older than 40 years. Details regarding patient demographics, preoperative assessment, management and tumour grade and stage were obtained from a prospectively maintained database., Results: One hundred and two of 287 patients (35.5%) were 40 or younger at presentation. Younger patients were more likely to present with less favourable histological features (52.0% vs 20.5% (P < 0.001)) and low rectal tumours (63.0% vs 50.0%) (P = 0.043), but were equally likely to undergo curative surgery compared to the older group (P = 0.629). Younger patients undergoing surgery had a higher pathological T stage (T0-2 18.9%, T3 62.3%, T4 19.7% vs 34.5%, 56.0%, 9.5%) (P = 0.027) and more advanced pathological N stage (N0 31.1%, N1 41.0%, N2 27.9% vs 53.4%, 26.7%, 17.2%) (P = 0.014)., Conclusion: The relative number of young patients with rectal cancer in this Indian series is higher than figures reported in western populations. The reasons for this are not clear. The histopathological features of rectal tumours in young patients in this study are consistent with similar studies in Western populations.
Published: 2009
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