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7. Assessment of Baseline Ultrawidefield Fluorescein Angiographic Quantitative Leakage Parameters with Ultrawidefield Fundus Features and Clinical Parameters in Diabetic Retinopathy in Protocol AA

Author

Harara, Abla M., Palacios, Angela N., Berger, Brian B., Corak, Boris, Luong, Bianca, Jhaveri, Chirag D., Wilson, Daniela Mariel, Jonna, Gowtham, Gunderson, Ivana, Hosein, Kimberly, Reid, Ryan M., Chexal, Saradha, Moore, Tori, Seidu, Tina A., Gatavaski, Valerie, Ren, Yong, Stern, Bradley A., Benvenutti, Celia E., Oude-Reimerink, Dinah S., Shaheen, Jenny, Grybas, John, Vitale-Kuhn, Julianne, Staffne, Jessica L., Ventimiglia, Katie M., Allis, Megan, Monk, Mary K., Thomas, Marc E., Massu, Nicole M., Edwards, Paul Andrew, Troszak, Tracy A., Irons, Amber N., Rego, Brittany, Han, Dennis P., Dorsey, Eleanor, Nelson, Erika, Sheppard, Hannah, Beringer, Joseph R., Kim, Judy E., Keller, Kristy L., Packard, Krissa L., Altmann, Marriner L., Goldberg, Mara, Chen, Nickolas, Winter, Pat A., Bourgeois, Shay, Jacobo, Samantha, Moebius, Stephanie J., Connor, Thomas B., Barwick, Vicki, Williams, Vesper V., Wirostko, William J., Ghuman, A. Thomas, Leslie, Anita H., Sharma, Ashish G., Kiesel, Cheryl, Dyshanowitz, Danielle, Knips, Eileen, Wing, Glenn, Walker, Joseph P., Raskauskas, Paul A., Kiesel, Raymond K., Schlossman, Deborah K., Weimann, Elizabeth S., Sharuk, George S., Kwak, Hanna, Cavallerano, Jerry D., Rhee, Jae W., Sampani, Konstantina, Tran, Katie V., Bestourous, Leila, Miranda, Linette, Krigman, Michael N., Stockman, Margaret E., Arrigg, Paul G., Cavicchi, Robert W., Kirby, Rita K., Glynn, Shireen, Papaconstantinou, Steve L., Shah, Sabera T., Murtha, Timothy J., Carli, William, Finch, Autumn K., Gentile, Angella K., Price, Angela K., Murphy, Brittany A., Rowland, Beverly O., Fleming, Christina J., Mahr, Courtney, Shore, Carol A., Browning, David, McClain, Donna, Breglio, Erica, Lester, Gina M., Herby, Jenna T., Bratcher, Kayla A., Clark, Loraine M., Jackson, Lisa A., Watson, Lynn, McOwen, Michael D., Punjabi, Omar S., Bojaj, Swann J., Ennis, Sarah A., Fredenberg, Sherry L., Jones, Taylor S., Ragin, Teneisha A., Balasubramaniam, Uma M., Ornelas, Blanca, Rodriquez, Brenda, Edwards, Carla, Carns, Danielle R., Tonner, Eileen E., Woo, Kisung, Richine, Len, MacCumber, Mathew W., Merrill, Pauline Townsend, Kociborski, Sarah, Harless, Ashley M., Harris, Charlotte, White, Lorraine, Maturi, Raj K., Asher, Julie, Walsh, Justin, Wheeler, Jeff, Milstead, Katie, Oliver, Kristina, Lovelady, Lisa, Anderson, Nicholas G., Coppola, Patricia, Lince, Raul E., Shuler, R. Keith, Morris, Steve, Oelrich, Sarah M., Gardner, Brandon S., Moore, Bob, Cain, Dennis, Donohue, Deborah, Emmert, David, Adeyemo, Kemi, Levin, Lisa K., Frey, Mary, Rhoton, Nick, Bressler, Susan, Solomon, Sharon D., Ford, Amy L., Hughes, Ashley, Brewer, Alisha N., Booth, JoAnn T., Lunsford, Keven W., Ukleya, Lauren D., Burris, Russ, Kingsley, Ronald M., Almeida, Shannon R., Icks, Sonny, Shah, Vinay A., Bergman, Vanessa A., Castellarin, Alessandro A., Shook, Aimee H., Walker, Aimee, Pieramici, Dante J., Hong, Gina, Avery, Kelly, McKee, Kate M., Giust, Matthew, Munoz, Marco A., Fishbein, Sarah, Camp, Alecia B., Baker, Carl W., Baker, Jil D., Sedberry, Kylie S., Lambert, Lynnette F., Orr, Margaret J., Alcaraz, Sonya L., Kettler, Samantha, Caldwell, Tracey M., Miller, Abigail, Dorr, Christine M., Hampton, G. Robert, Brown, Jamin S., Barker, Jeffrey P., Rosenberg, Kevin I., Kwasniewski, Lynn M., Sienkiewycz, Laurie J., Spuches, Lisa, Manley, Michelle L., Robarge, Nicole E., DeSantis, Stefanie R., DeForge, Teresa M., Brucker, Alexander J., Kim, Benjamin J., Berger, Jim M., DuPont, Joan C., Drossner, Sheri, Freeman, Sara, Studebaker, Ashley, Payne, John F., Wells, John A., Spivey, Robbin, Ogbuewu, Tiffany N., Swinford, Tiffany R., Guillory, Adrienne, Hutson, Amy, Schefler, Amy C., Shah, Ankoor R., Almanza, Belinda A., Dives, Brenda, Richter, Beau A., Stoever, Cary A., Brown, David M., Foerster, Danee, Garcia, David, Rodriguez, Diana, Park, Daniel, Chen, Eric, Kegley, Eric N., Quellar, Elizabeth, Twining, Garret L., Koger-Grifaldo, Heather, Ortega, Ilsa, Carranza, Jolene, Major, James C., Williamson, Kimberly, Burt, Lindsay, Salinas, Luis R., Wolff, Lisa M., Benz, Matthew S., Estes, Maura A., James, Miranda F., Berry, Meredith, Vela, Melina, Landaverde, Nubia, Webb, Nina A., Fish, Richard H., Kim, Rosa Y., Yee, Rebecca, Karani, Sadia Y., Supapo, Stacy M., Dodel, Tamara L., McCoy, Tyneisha, Wong, Tien P., Sneed, Veronica A., Barnhart, Cassandra J., Cantrell, Debra, DuBose, Elizabeth L., Sharpe, Houston P., Ulrich, Jan Niklas, Bhansali, Kanika A., Esquejo, Rona Lyn, Garg, Seema, Grout, Sean, McKinney, Allen, Bobbitt, Brenda J., Wendel, Ceara L., Fagan, Damanda F., Andrews, Jacqueline, Holmes, Krystal Nikki, Seyez, Karen L., Williamson, Kimberly A., Moinfar, Nader, Walters, Paige N., Carlton, Steve, Rehling, Shannon M., Williams, Shana E., Reed, Tiara L., VandeVelde, Amber R., Yeager, Frank T., Fox, Gregory M., Batlle, Ivan R., Bruce, Kiersten, Pippin, Katherine, Ainley, Lexie R., Singh, Ravi S.J., Adamo, Ashley M., Guardado, Adrian, Patel, Apurva K., Puckett, Brian S., Hoerner, Christine, Ma, Colin, Clark, David J., Flato, Inessa M., Cohen, Joshua, Charpentier, Margaret E., Kopfer, Marcia, Peters, Mark A., Smith, Pualani, Tlucek, Paul S., Hobbs, Stephen, Ho, Stephanie L., Metzger, Ashley M., McCalla, Alesia K., Thompson, Amy, Ringrose, Christine, Sandler, Dallas R., Leder, Henry A., Belz, Jennifer L., Starr, JoAnn, Simmons, Jennifer L., Orr, Peggy R., Sotirakos, Peter, Singletary, Pamela V., Cain, Terri, Coffey, Teresa, Carter, Tiffany M., Robinson, Twyla J., Shah, Chirag P., Cammarata, Dominique, Kruger, Jennifer L., Colegrove, Lindsey, Graham, Margie, Gleason, Shane T., Noel, Bryan, Damron, Catherine, Holcomb, Diana M., Slade, Edward A., Van Arsdall, Jeanne, Bicknell, Lisa, Buck, Michelle, Stone, Thomas W., Farooq, Amina, Parsons, Brook, Singh, Harinderjit, Ivey, Ken, Foster, Lindsay Allison, Woodward, Michele, Ortiz, Siobhan O., Bailey, Thomas, Mynampati A, Bharani Krishna, White, Cheryl L., Hamdani, Ghulam Shabbir, Smith, Jazzmin N., Chalam, Kakarla V., Sambhav, Kumar, Babaria, Romesh, Grover, Sandeep, Carroll, Catherine, Chau, Felix Y., Lim, Jennifer I., Talasnik, Lauren A., Janowicz, Mark, Stankovic, Natasa, Berlatsky, Sarah L., Niec, Marcia, Sun, Jie, Johnson, Tametha, Ovando, Yesenia, Nakoski, Brenda, Mein, Calvin E., Wienecke, Christopher Sean, Castillo, Elaine, Baker, Jaynee, San Roman, Jonathan, Adams, Lydia, Kirschbaum, Lita, Chica, Moises A., Cloudt, Sara L., Moore, Tori R., Sabates, Felix N., Gallimore, Gary S., Chen, Yin C., Swann, Adrienne C., Cadwell, Deborah M., Diddie, Kenneth R., Boisvert, Taryn F., Tessau, Carrie D., Bowers, Jack, Nielsen, Jared S., Rostvold, Jay, Spillman, Jamie, Alliman, Kyle J., Boender, Lisa M., Johnson, Marilyn A., Parker, Marianne, Bix, Paula L., Ridgway, Spencer D., Woehl, Tami Jo, Stonewall, Whitney, Brown, Christopher M., Lema, Gareth M.C., Wiechelt, Luann, Yoganathan, Pradeepa, Boglione, Sandra L., Montesclaros, Chris A., Mangham, Cory, Karsaliya, Gopal, Le, Phillip V., Wong, Robert W., Godfrey, Anne Marie, Kuzmanovic, Aleksandra, Kirker, Andrew William, Harrison, Bryan, Forooghian, Farzin, Elvena, Garnet Louise, Hall, Laura J., Turhal, Bilgin, Brown, Ian, Kotei, Isaac A., Chen, Lina, Brent, Michael Henry, Moon, Michelle, Sutakovic, Olivera, Chang, Angela, Godfrey, Anne-Marie, Albiani, David, Maberley, David A.L., Navajas, Eduardo Vitor, Grant, Kelly, Tran, Khoi A., Jovanovic, Mira, Cao, Sijia, Wiens, Theresa, Kozbial, Andrzej, Orlin, Anton, Lenane, Courtney Nichole, Herder, Susan P., Kiss, Szilard, Reeves, Tom, Cruess, Alan F., Dean, Andrea, Hoskin-Mott, Ann, Morrison, Christine, Caldwell, Meggie D., Hynes, Mitzi, Gupta, R. Rishi, Durling, Stacey, MacDonnell, Trina, Beck, Roy W., Baptista, Alyssa, Beaulieu, Wesley T., Calhoun, Claire T., Constantine, Sharon R., Correia, Isabella, Dale, Brian B., Dupre, Simone S., Franklin, Crystal A., Galusic, Sandra, Huggins, Meagan, Hunter, Brenda L., Johnson, Paula A., Josic, Kristin, Kelly, Brittany, Maguire, Maureen G., Meadows, Britney, Stockdale, Cynthia R., Zokruah, Alice, Bhargava, Sangeeta, Barkmeier, Andrew J., Baskin, Darrell, Blodi, Barbra, Chew, Emily, Ferris, Frederick L., Jaffe, Glenn J., Bressler, Neil M., Lujan, Brandon, Tolls, Dorothy, Sheridan, Daniel, Pitoc, Cloyd M., Anne C Aquino, Lizzie, Salva, Claude Michael G., Lewis, Drew, Stainback, Jeffery, Makkena, Vijaya, Winter, Katrina, Mora, Adiel, Harrington, Chris, Vinh, Doc-Lap, Ehlers, Justis P., Yordi, Sari, Martin, Alison, Srivastava, Sunil K., and Sun, Jenifer K.

Published
2024
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9. A Generative Neural Network Framework for Automated Software Testing

Author

Joffe, Leonid and Clark, David J.

Subjects
Computer Science - Software Engineering, Computer Science - Machine Learning
Abstract

Search Based Software Testing (SBST) is a popular automated testing technique which uses a feedback mechanism to search for faults in software. Despite its popularity, it has fundamental challenges related to the design, construction and interpretation of the feedback. Neural Networks (NN) have been hugely popular in recent years for a wide range of tasks. We believe that they can address many of the issues inherent to common SBST approaches. Unfortunately, NNs require large and representative training datasets. In this work we present an SBST framework based on a deconvolutional generative neural network. Not only does it retain the beneficial qualities that make NNs appropriate for SBST tasks, it also produces its own training data which circumvents the problem of acquiring a training dataset that limits the use of NNs. We demonstrate through a series of experiments that this architecture is possible and practical. It generates diverse, sensible program inputs, while exploring the space of program behaviours. It also creates a meaningful ordering over program behaviours and is able to find crashing executions. This is all done without any prior knowledge of the program. We believe this proof of concept opens new directions for future work at the intersection of SBST and neural networks.

Published
2020

13. Skp, Cullin, F-box (SCF)-Met30 and SCF-Cdc4-Mediated Proteolysis of CENP-A Prevents Mislocalization of CENP-A for Chromosomal Stability in Budding Yeast.

Author

Au, Wei-Chun, Zhang, Tianyi, Mishra, Prashant K, Eisenstatt, Jessica R, Walker, Robert L, Ocampo, Josefina, Dawson, Anthony, Warren, Jack, Costanzo, Michael, Baryshnikova, Anastasia, Flick, Karin, Clark, David J, Meltzer, Paul S, Baker, Richard E, Myers, Chad, Boone, Charles, Kaiser, Peter, and Basrai, Munira A

Subjects
Centromere, Saccharomyces cerevisiae, Chromosomal Instability, Ubiquitin-Protein Ligase Complexes, Ubiquitin-Protein Ligases, SKP Cullin F-Box Protein Ligases, F-Box Proteins, Cell Cycle Proteins, DNA-Binding Proteins, Saccharomyces cerevisiae Proteins, Chromosomal Proteins, Non-Histone, Chromosome Segregation, Ubiquitination, Proteolysis, Protein Domains, Chromosomal Proteins, Non-Histone, Genetics, Developmental Biology
Abstract

Restricting the localization of the histone H3 variant CENP-A (Cse4 in yeast, CID in flies) to centromeres is essential for faithful chromosome segregation. Mislocalization of CENP-A leads to chromosomal instability (CIN) in yeast, fly and human cells. Overexpression and mislocalization of CENP-A has been observed in many cancers and this correlates with increased invasiveness and poor prognosis. Yet genes that regulate CENP-A levels and localization under physiological conditions have not been defined. In this study we used a genome-wide genetic screen to identify essential genes required for Cse4 homeostasis to prevent its mislocalization for chromosomal stability. We show that two Skp, Cullin, F-box (SCF) ubiquitin ligases with the evolutionarily conserved F-box proteins Met30 and Cdc4 interact and cooperatively regulate proteolysis of endogenous Cse4 and prevent its mislocalization for faithful chromosome segregation under physiological conditions. The interaction of Met30 with Cdc4 is independent of the D domain, which is essential for their homodimerization and ubiquitination of other substrates. The requirement for both Cdc4 and Met30 for ubiquitination is specifc for Cse4; and a common substrate for Cdc4 and Met30 has not previously been described. Met30 is necessary for the interaction between Cdc4 and Cse4, and defects in this interaction lead to stabilization and mislocalization of Cse4, which in turn contributes to CIN. We provide the first direct link between Cse4 mislocalization to defects in kinetochore structure and show that SCF-mediated proteolysis of Cse4 is a major mechanism that prevents stable maintenance of Cse4 at non-centromeric regions, thus ensuring faithful chromosome segregation. In summary, we have identified essential pathways that regulate cellular levels of endogenous Cse4 and shown that proteolysis of Cse4 by SCF-Met30/Cdc4 prevents mislocalization and CIN in unperturbed cells.

Published
2020

16. Prevalence and outcomes of patients with SMuRF-less acute coronary syndrome undergoing percutaneous coronary intervention

Author

Ball, Jocasta, primary, Dinh, Diem T, additional, Brennan, Angela, additional, Ajani, Andrew, additional, Clark, David J, additional, Freeman, Melanie, additional, Oqueli, Ernesto, additional, Hiew, Chin, additional, Nanayakkara, Shane, additional, Walton, Antony, additional, Shaw, James A, additional, Chan, William, additional, Reid, Christopher M, additional, and Stub, Dion, additional

Published
2024
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17. Patient preference and acceptability of self-sampling for cervical screening in colposcopy clinic attenders: A cross-sectional semi-structured survey

Author

Webb, Sophie, primary, Mat Ali, Nafeesa, additional, Sawyer, Amy, additional, Clark, David J., additional, Brown, Megan A., additional, Augustin, Yolanda, additional, Woo, Yin Ling, additional, Khoo, Su Pei, additional, Hargreaves, Sally, additional, Staines, Henry M., additional, Krishna, Sanjeev, additional, and Hayes, Kevin, additional

Published
2024
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18. Resting state brain network segregation is associated with walking speed and working memory in older adults

Author

Sato, Sumire D., primary, Shah, Valay A., additional, Fettrow, Tyler, additional, Hall, Kristina G., additional, Tays, Grant D., additional, Cenko, Erta, additional, Roy, Arkaprava, additional, Clark, David J., additional, Ferris, Daniel P., additional, Hass, Chris J., additional, Manini, Todd M., additional, and Seidler, Rachael D., additional

Published
2024
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20. tRNA Genes Affect Chromosome Structure and Function via Local Effects.

Author

Hamdani, Omar, Dhillon, Namrita, Hsieh, Tsung-Han S, Fujita, Takahiro, Ocampo, Josefina, Kirkland, Jacob G, Lawrimore, Josh, Kobayashi, Tetsuya J, Friedman, Brandon, Fulton, Derek, Wu, Kenneth Y, Chereji, Răzvan V, Oki, Masaya, Bloom, Kerry, Clark, David J, Rando, Oliver J, and Kamakaka, Rohinton T

Subjects
Chromosomes, Cell Nucleus, Chromatin, Heterochromatin, Saccharomyces cerevisiae, Transcription Factors, TFIII, Saccharomyces cerevisiae Proteins, RNA, Transfer, Chromatin Assembly and Disassembly, Binding Sites, SMC proteins, Saccharomyces cerevisiae, chromatin, chromosome structure, gene silencing, nucleosome, tDNA, Transcription Factors, TFIII, RNA, Transfer, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

The genome is packaged and organized in an ordered, nonrandom manner, and specific chromatin segments contact nuclear substructures to mediate this organization. tRNA genes (tDNAs) are binding sites for transcription factors and architectural proteins and are thought to play an important role in the organization of the genome. In this study, we investigate the roles of tDNAs in genomic organization and chromosome function by editing a chromosome so that it lacked any tDNAs. Surprisingly our analyses of this tDNA-less chromosome show that loss of tDNAs does not grossly affect chromatin architecture or chromosome tethering and mobility. However, loss of tDNAs affects local nucleosome positioning and the binding of SMC proteins at these loci. The absence of tDNAs also leads to changes in centromere clustering and a reduction in the frequency of long-range HML-HMR heterochromatin clustering with concomitant effects on gene silencing. We propose that the tDNAs primarily affect local chromatin structure, which results in effects on long-range chromosome architecture.

Published
2019

26. Management of Acute Coronary Syndromes in Older People: Comprehensive Review and Multidisciplinary Practice-Based Recommendations.

Author

Narendren, Ahthavan, Whitehead, Natalie, Burrell, Louise M., Yudi, Matias B., Yeoh, Julian, Jones, Nicholas, Weinberg, Laurence, Miles, Lachlan F., Lim, Han S., Clark, David J., Al-Fiadh, Ali, Farouque, Omar, and Koshy, Anoop N.

Subjects
OLDER people, ACUTE coronary syndrome, OLDER patients, OCTOGENARIANS, CORONARY artery disease
Abstract

Managing health care for older adults aged 75 years and older can pose unique challenges stemming from age-related physiological differences and comorbidities, along with elevated risk of delirium, frailty, disability, and polypharmacy. This review is aimed at providing a comprehensive analysis of the management of acute coronary syndromes (ACS) in older patients, a demographic substantially underrepresented in major clinical trials. Because older patients often exhibit atypical ACS symptoms, a nuanced diagnostic and risk stratification approach is necessary. We aim to address diagnostic challenges for older populations and highlight the diminished sensitivity of traditional symptoms with age, and the importance of biomarkers and imaging techniques tailored for older patients. Additionally, we review the efficacy and safety of pharmacological agents for ACS management in older people, emphasizing the need for a personalized and shared decision-making approach to treatment. This review also explores revascularization strategies, considering the implications of invasive procedures in older people, and weighing the potential benefits against the heightened procedural risks, particularly with surgical revascularization techniques. We explore the perioperative management of older patients experiencing myocardial infarction in the setting of noncardiac surgeries, including preoperative risk stratification and postoperative care considerations. Furthermore, we highlight the critical role of a multidisciplinary approach involving cardiologists, geriatricians, general and internal medicine physicians, primary care physicians, and allied health, to ensure a holistic care pathway in this patient cohort. [ABSTRACT FROM AUTHOR]

Published
2024
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27. Electrical brain activity during human walking with parametric variations in terrain unevenness and walking speed

Author

Liu, Chang, primary, Downey, Ryan J., additional, Salminen, Jacob S., additional, Arvelo Rojas, Sofia, additional, Richer, Natalie, additional, Pliner, Erika M., additional, Hwang, Jungyun, additional, Cruz-Almeida, Yenisel, additional, Manini, Todd M., additional, Hass, Chris J., additional, Seidler, Rachael D., additional, Clark, David J., additional, and Ferris, Daniel P., additional

Published
2024
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34. Graft Patency and Clinical Outcomes in Patients With Radial Artery Grafts Previously Instrumented for Cardiac Catheterization.

Author

Hamilton, Garry W., Theuerle, James, Chye, David, Bhaskar, Jayapadman, Seevanayagam, Siven, Johns, Hannah, Churilov, Leonid, Yeoh, Julian, Yudi, Matias B., Brown, Louise, Raman, Jaishankar, Clark, David J., Hare, David L., and Farouque, Omar

Abstract

BACKGROUND: While transradial access is favored for cardiac catheterization, the radial artery (RA) is increasingly preferred for coronary artery bypass grafting. Whether the RA is suitable for use as a graft following instrumentation for transradial access remains uncertain. METHODS: Consecutive patients from 2015 to 2019 who underwent coronary artery bypass grafting using both the left and right RAs as grafts were included. Instrumented RAs underwent careful preoperative assessment for suitability. The clinical analysis was stratified by whether patients received an instrumented RA graft (instrumented versus noninstrumented groups). Eligible patients with both instrumented and noninstrumented RAs underwent computed tomography coronary angiography to evaluate graft patency. The primary outcome was a within-patient paired analysis of graft patency comparing instrumented to noninstrumented RA grafts. RESULTS: Of the 1123 patients who underwent coronary artery bypass grafting, 294 had both the left and right RAs used as grafts and were included. There were 126 and 168 patients in the instrumented and noninstrumented groups, respectively. Baseline characteristics and perioperative outcomes were comparable. The rate of major adverse cardiac events at 2 years following coronary artery bypass grafting was 2.4% in the instrumented group and 5.4% in the noninstrumented group (hazard ratio, 0.44 [95% CI, 0.12-1.61]; P=0.19). There were 50 patients included in the graft patency analysis. At a median follow-up of 4.3 (interquartile range, 3.7-4.5) years, 40/50 (80%) instrumented and 41/50 (82%) noninstrumented grafts were patent (odds ratio, 0.86 [95% CI, 0.29-2.52]; P>0.99). No significant differences were observed in the luminal diameter or cross-sectional area of the instrumented and noninstrumented RA grafts. CONCLUSIONS: There was no evidence found in this study that RA graft patency was affected by prior transradial access, and the use of an instrumented RA was not associated with worse outcomes in the exploratory clinical analysis. Although conduits must be carefully selected, prior transradial access should not be considered an absolute contraindication to the use of the RA as a bypass graft. [ABSTRACT FROM AUTHOR]

Published
2024
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35. Prefrontal cortical activity during uneven terrain walking in younger and older adults.

Author

Jungyun Hwang, Chang Liu, Winesett, Steven P., Chatterjee, Sudeshna A., Gruber, Anthony D., Swanson, Clayton W., Manini, Todd M., Hass, Chris J., Seidler, Rachael D., Ferris, Daniel P., Roy, Arkaprava, and Clark, David J.

Subjects
CROSS-sectional method, RESEARCH funding, INDEPENDENT living, DATA analysis, TASK performance, PREFRONTAL cortex, FUNCTIONAL assessment, LOGISTIC regression analysis, NEUROSCIENCES, AGE distribution, NEAR infrared spectroscopy, CHI-squared test, WALKING, TREADMILLS, AGING, ONE-way analysis of variance, STATISTICS, DATA analysis software, COGNITION, PHYSICAL mobility, ADULTS, OLD age
Abstract

Introduction: Walking in complex environments increases the cognitive demand of locomotor control; however, our understanding of the neural mechanisms contributing to walking on uneven terrain is limited. We used a novel method for altering terrain unevenness on a treadmill to investigate the association between terrain unevenness and cortical activity in the prefrontal cortex, a region known to be involved in various cognitive functions. Methods: Prefrontal cortical activity was measured with functional near infrared spectroscopy while participants walked on a novel custom-made terrain treadmill surface across four different terrains: flat, low, medium, and high levels of unevenness. The assessments were conducted in younger adults, older adults with better mobility function and older adults with worse mobility function. Mobility function was assessed using the Short Physical Performance Battery. The primary hypothesis was that increasing the unevenness of the terrain would result in greater prefrontal cortical activation in all groups. Secondary hypotheses were that heightened prefrontal cortical activation would be observed in the older groups relative to the younger group, and that prefrontal cortical activation would plateau at higher levels of terrain unevenness for the older adults with worse mobility function, as predicted by the Compensation Related Utilization of Neural Circuits Hypothesis. Results: The results revealed a significant main effect of terrain, indicating a significant increase in prefrontal cortical activation with increasing terrain unevenness during walking in all groups. A significant main effect of group revealed that prefrontal cortical activation was higher in older adults with better mobility function compared to younger adults and older adults with worse mobility function in all pooled terrains, but there was no significant difference in prefrontal cortical activation between older adults with worse mobility function and younger adults. Contrary to our hypothesis, the older group with better mobility function displayed a sustained increase in activation but the other groups did not, suggestive of neural compensation. Additional findings were that task-related increases in prefrontal cortical activation during walking were lateralized to the right hemisphere in older adults with better mobility function but were bilateral in older adults with worse mobility function and younger adults. Discussion: These findings support that compared to walking on a flat surface, walking on uneven terrain surfaces increases demand on cognitive control resources as measured by prefrontal cortical activation. [ABSTRACT FROM AUTHOR]

Published
2024
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41. Does Falls Efficacy Influence the Relationship Between Forward and Backward Walking Speed After Stroke?

Author

Bansal, Kanika, Clark, David J., Fox, Emily J., and Rose, Dorian K.

Subjects
Falls (Accidents) -- Risk factors, Stroke (Disease) -- Complications and side effects, Walking -- Health aspects
Abstract

Objective. Forward walking speed (FWS) is known to be an important predictor of mobility, falls, and falls-related efficacy poststroke. However, backward walking speed (BWS) is emerging as an assessment tool to reveal mobility deficits in people poststroke that may not be apparent with FWS alone. Since backward walking is more challenging than forward walking, falls efficacy may play a role in the relationship between one's preferred FWS and BWS. We tested the hypothesis that people with lower falls efficacy would have a stronger positive relationship between FWS and BWS than those with higher falls efficacy. Methods. Forty-five individuals (12.9 [+ or -] 5.6 months poststroke) participated in this observational study. We assessed FWS with the 10-meter walk test and BWS with the 3-meter backward walk test. The modified Falls-Efficacy Scale (mFES) quantified falls efficacy. A moderated regression analysis examined the hypothesis. Results. FWS was positively associated with BWS ([R.sup.2] = 0.26). The addition of the interaction term FWS x mFES explained 7.6% additional variance in BWS. As hypothesized, analysis of the interaction revealed that people with lower falls efficacy (mFES [less than or equal to] 6.6) had a significantly positive relationship between their preferred FWS and BWS, whereas people with higher falls efficacy (mFES > 6.6) had no relationship between their walking speed in the 2 directions. Conclusions. FWS is positively related to BWS poststroke, but this relationship is influenced by one's perceived falls efficacy. Our results suggest that BWS can be predicted from FWS in people with lower falls efficacy, but as falls efficacy increases, BWS becomes a separate and unassociated construct from FWS. Impact. This study provides unique evidence that the degree of falls efficacy significantly influences the relationship between FWS and BWS poststroke. Physical therapists should examine both FWS and BWS in people with higher falls efficacy, but further investigation is warranted for those with lower falls efficacy. Keywords: Gait, Rehabilitation, Self-Efficacy, Stroke, Introduction Stroke is the number one cause of long-term disability in the United States. (1) Nearly 7.2 million Americans were reported to be living with stroke between 2011 and 2014. [...]

Published
2021
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42. Comparative Effects of Light or Heavy Resistance Power Training for Improving Lower Extremity Power and Physical Performance in Mobility-Limited Older Adults

Author

Reid, Kieran F, Martin, Kimberly I, Doros, Gheorghe, Clark, David J, Hau, Cynthia, Patten, Carolynn, Phillips, Edward M, Frontera, Walter R, and Fielding, Roger A

Subjects
Neurosciences, Rehabilitation, Physical Rehabilitation, Prevention, Clinical Research, Aging, Aged, Aged, 80 and over, Electromyography, Female, Humans, Isometric Contraction, Lower Extremity, Male, Mobility Limitation, Muscle Strength, Quadriceps Muscle, Resistance Training, Single-Blind Method, Tomography, X-Ray Computed, Mobility limitations, exercise interventions, muscle power, high-velocity resistance training, high-velocity resistance training., Clinical Sciences, Gerontology
Abstract

BackgroundWe compared the effects of two uniquely different lower extremity power training interventions on changes in muscle power, physical performance, neuromuscular activation, and muscle cross sectional area in mobility-limited older adults.MethodsFifty-two subjects (78±5 years, short physical performance battery score: 8.1±1) were randomized to either 16 weeks of progressive high velocity resistance training performed at low external resistance (40% of the 1-repetition maximum [1-RM] [LO]) or high external resistance (70% of 1RM [HI]). Both groups completed three sets of leg and knee extension exercises at maximum voluntary velocity, two times per week. Neuromuscular activation was assessed using surface electromyography and muscle cross sectional area (CSA) was measured using computed tomography.ResultsAt 16 weeks, LO and HI exhibited significant and similar within-group increases of leg extensor peak power (~34% vs ~42%), strength (~13% vs ~19%), and SPPB score (1.4±0.3 vs 1.8±0.3 units), respectively (all P < .03). Improvements in neuromuscular activation occurred in LO (P = .03) while small gains in mid-thigh muscle CSA were detected in LO (1.6%, P = .35) and HI (2.1%, P = .17). No significant between-group differences were evident for any measured parameters (all P > .25).ConclusionsHigh velocity resistance training with low external resistance yields similar improvements in muscle power and physical performance compared to training with high external resistance in mobility-limited elders. These findings may have important implications for optimizing exercise interventions for older adults with mobility limitations.

Published
2015

46. Does quadriceps neuromuscular activation capability explain walking speed in older men and women?

Author

Clark, David J, Reid, Kieran F, Patten, Carolynn, Phillips, Edward M, Ring, Sarah A, Wu, Samuel S, and Fielding, Roger A

Subjects
Aging, Neurosciences, Clinical Research, 1.1 Normal biological development and functioning, Underpinning research, Musculoskeletal, Aged, Aged, 80 and over, Electromyography, Exercise Test, Female, Humans, Male, Muscle Contraction, Neuromuscular Junction, Quadriceps Muscle, Sex Characteristics, Walking, Nervous system, Muscle, Mobility, Medical and Health Sciences, Gerontology
Abstract

Age-related impairment of neuromuscular activation has been shown to contribute to weakness in older adults. However, it is unclear to what extent impaired neuromuscular activation independently accounts for decline of mobility function. The hypothesis of this study is that the capability to produce rapid neuromuscular activation during maximal effort leg muscle contractions will be shown to be an independent predictor of mobility function in older men and women after accounting for muscle size and adiposity, body composition and age. Twenty six older men and eighteen older women (aged 70-85years) participated in this study. Mobility function was assessed by the 400-m walk test. Neuromuscular activation of the quadriceps muscle group was assessed by surface electromyography ("rate of EMG rise"). Thigh muscle cross sectional area and adiposity were assessed by computed tomography. In males, univariate regression analysis revealed strong associations between walking speed and a number of predictors including age (p

Published
2014

47. Longitudinal decline of lower extremity muscle power in healthy and mobility-limited older adults: influence of muscle mass, strength, composition, neuromuscular activation and single fiber contractile properties

Author

Reid, Kieran F, Pasha, Evan, Doros, Gheorghe, Clark, David J, Patten, Carolynn, Phillips, Edward M, Frontera, Walter R, and Fielding, Roger A

Subjects
Aging, Clinical Research, Musculoskeletal, Aged, Aged, 80 and over, Case-Control Studies, Female, Humans, Longitudinal Studies, Lower Extremity, Male, Mobility Limitation, Muscle Contraction, Muscle Fibers, Skeletal, Muscle Strength, Quadriceps Muscle, Tomography, X-Ray Computed, Lower extremity muscle power, Single muscle fiber, Longitudinal, Human Movement and Sports Sciences, Sport Sciences
Abstract

PurposeThis longitudinal study examined the major physiological mechanisms that determine the age-related loss of lower extremity muscle power in two distinct groups of older humans. We hypothesized that after ~3 years of follow-up, mobility-limited older adults (mean age: 77.2 ± 4, n = 22, 12 females) would have significantly greater reductions in leg extensor muscle power compared to healthy older adults (74.1 ± 4, n = 26, 12 females).MethodsMid-thigh muscle size and composition were assessed using computed tomography. Neuromuscular activation was quantified using surface electromyography and vastus lateralis single muscle fibers were studied to evaluate intrinsic muscle contractile properties.ResultsAt follow-up, the overall magnitude of muscle power loss was similar between groups: mobility-limited: -8.5 % vs. healthy older: -8.8 %, P > 0.8. Mobility-limited elders had significant reductions in muscle size (-3.8 %, P < 0.01) and strength (-5.9 %, P < 0.02), however, these parameters were preserved in healthy older (P ≥ 0.7). Neuromuscular activation declined significantly within healthy older, but not in mobility-limited participants. Within both groups, the cross-sectional areas of type I and IIA muscle fibers were preserved while substantial increases in single fiber peak force (>30 %), peak power (>200 %) and unloaded shortening velocity (>50 %) were elicited at follow-up.ConclusionDifferent physiological mechanisms contribute to the loss of lower extremity muscle power in healthy older and mobility-limited older adults. Neuromuscular changes may be the critical early determinant of muscle power deficits with aging. In response to major whole muscle decrements, major compensatory mechanisms occur within the contractile properties of surviving single muscle fibers in an attempt to restore overall muscle power and function with advancing age.

Published
2014

49. Electrical Brain Activity during Human Walking with Parametric Variations in Terrain Unevenness and Walking Speed

Author

Liu, Chang, primary, Downey, Ryan J., additional, Salminen, Jacob S., additional, Rojas, Sofia Arvelo, additional, Richer, Natalie, additional, Pliner, Erika M., additional, Hwang, Jungyun, additional, Cruz-Almeida, Yenisel, additional, Manini, Todd M., additional, Hass, Chris J., additional, Seidler, Rachael D., additional, Clark, David J., additional, and Ferris, Daniel P., additional

Published
2023
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