Digital Commons Network^™

Genetic Associations Between Modifiable Risk Factors And Alzheimer Disease, Jiao Luo, Jesper Qvist Thomassen, Céline Bellenguez, Benjamin Grenier-Boley, Itziar De Rojas, Atahualpa Castillo, Kayenat Parveen, Fahri Küçükali, Aude Nicolas, Oliver Peters, Anja Schneider, Martin Dichgans, Dan Rujescu, Norbert Scherbaum, Deckert Jürgen, Steffi Riedel-Heller, Lucrezia Hausner, Laura Molina Porcel, Emrah Düzel, Timo Grimmer, Jens Wiltfang, Stefanie Heilmann-Heimbach, Susanne Moebus, Thomas Tegos, Nikolaos Scarmeas, Jordi Clarimon, Fermin Moreno, Jordi Pérez-Tur, María J Bullido, Pau Pastor, Raquel Sánchez-Valle, Victoria Álvarez, Mercè Boada, Pablo García-González, Raquel Puerta, Pablo Mir, Luis M Real, Gerard Piñol-Ripoll, Jose María García-Alberca, Jose Luís Royo, Eloy Rodriguez-Rodriguez, Hilkka Soininen, Teemu Kuulasmaa, Alexandre De Mendonça, Shima Mehrabian, Jakub Hort, Martin Vyhnalek, Sven Van Der Lee, Caroline Graff, Goran Papenberg, Vilmantas Giedraitis, Anne Boland, Delphine Bacq-Daian, Jean-François Deleuze, Gael Nicolas, Carole Dufouil, Florence Pasquier, Olivier Hanon, Stéphanie Debette, Edna Grünblatt, Julius Popp, Luisa Benussi, Daniela Galimberti, Beatrice Arosio, Patrizia Mecocci, Vincenzo Solfrizzi, Lucilla Parnetti, Alessio Squassina, Lucio Tremolizzo, Barbara Borroni, Benedetta Nacmias, Sandro Sorbi, Paolo Caffarra, Davide Seripa, Innocenzo Rainero, Antonio Daniele, Carlo Masullo, Gianfranco Spalletta, Julie Williams, Philippe Amouyel, Frank Jessen, Patrick Kehoe, Magda Tsolaki, Giacomina Rossi, Pascual Sánchez-Juan, Kristel Sleegers, Martin Ingelsson, Ole A Andreassen, Mikko Hiltunen, Cornelia Van Duijn, Rebecca Sims, Wiesje Van Der Flier, Agustín Ruiz, Alfredo Ramirez, Jean-Charles Lambert, Ruth Frikke-Schmidt

Faculty, Staff and Students Publications

IMPORTANCE: An estimated 40% of dementia is potentially preventable by modifying 12 risk factors throughout the life course. However, robust evidence for most of these risk factors is lacking. Effective interventions should target risk factors in the causal pathway to dementia.

OBJECTIVE: To comprehensively disentangle potentially causal aspects of modifiable risk factors for Alzheimer disease (AD) to inspire new drug targeting and improved prevention.

DESIGN, SETTING, AND PARTICIPANTS: This genetic association study was conducted using 2-sample univariable and multivariable mendelian randomization. Independent genetic variants associated with modifiable risk factors were selected as instrumental variables from genomic consortia. Outcome data for …

Elevated Bile Acids Are Associated With Left Ventricular Structural Changes In Biliary Atresia, Manpreet K Virk, Muhammad Umair M Mian, Dalia A Bashir, John K Wilkes, Tobias Schlingman, Saul Flores, Curtis Kennedy, Fong Lam, Ayse A Arikan, Trung Nguyen, Krupa Mysore, Nhu Thao Nguyen Galvan, Jorge Coss-Bu, Saul J Karpen, Sanjiv Harpavat, Moreshwar S Desai

Faculty, Staff and Students Publications

BACKGROUND: In children with biliary atresia (BA), pathologic structural changes within the heart, which define cirrhotic cardiomyopathy, are associated with adverse perioperative outcomes. Despite their clinical relevance, little is known about the pathogenesis and triggers of pathologic remodeling. Bile acid excess causes cardiomyopathy in experimental cirrhosis, but its role in BA is poorly understood.

METHODS: Echocardiographic parameters of left ventricular (LV) geometry [LV mass (LVM), LVM indexed to height, left atrial volume indexed to BSA (LAVI), and LV internal diameter (LVID)] were correlated with circulating serum bile acid concentrations in 40 children (52% female) with BA listed for transplantation. A …

Monte Carlo-Derived 99m Tc Uptake Quantification With Commercial Planar Mbi: Absolute Tumor Activity, Benjamin P Lopez, Srinivas Cheenu Kappadath

Faculty, Staff and Student Publications

BACKGROUND: Molecular breast imaging (MBI) of 99mTc-sestamibi is an emerging adjunct qualitative tool in the detection and diagnosis of breast cancer.

PURPOSE: This work outlines the development and performance evaluation of a methodology to absolutely quantify tumor 99mTc activity uptake using a commercially available dual-headed MBI system by implementing corrections for background, scatter, attenuation, and detector characteristics.

METHODS: A validated Monte Carlo application of a commercial MBI system was used to simulate over 7000 unique acquisitions of spherical and ellipsoidal tumors in breast tissue. Tumor absolute activity was calculated following background, scatter, and attenuation corrections of tumor region of interest …

Depression, Stress And Regional Cerebral Blood Flow, Joshua Chiappelli, Bhim M Adhikari, Mark D Kvarta, Heather A Bruce, Eric L Goldwaser, Yizhou Ma, Shuo Chen, Seth Ament, Alan R Shuldiner, Braxton D Mitchell, Peter Kochunov, Danny Jj Wang, L Elliot Hong

Faculty, Staff and Student Publications

Decreased cerebral blood flow (CBF) may be an important mechanism associated with depression. In this study we aimed to determine if the association of CBF and depression is dependent on current level of depression or the tendency to experience depression over time (trait depression), and if CBF is influenced by depression-related factors such as stressful life experiences and antidepressant medication use. CBF was measured in 254 participants from the Amish Connectome Project (age 18-76, 99 men and 154 women) using arterial spin labeling. All participants underwent assessment of symptoms of depression measured with the Beck Depression Inventory and Maryland Trait …

The Gendered Experience Of Female Resident Assistants, Christa Rahl

Department of Educational Administration: Dissertations, Theses, and Student Research

This paper sought to answer, “What is it like to be a female resident assistant (RA) in a society that has historically privileged men?” I structured this as a phenomenology within the transformative paradigm. I interviewed four participants twice with a prompt between interviews and one participant once. These participants were at least 19 years old and had held been an RA for at least one school year during the last five years.

I worked in the realm of Joan Acker’s (1990) theory of gendered organizations. I specifically had findings within the constructions she wrote about such as the division …

Outcomes Following Extracorporeal Membrane Oxygenation For Severe Covid-19 In Pregnancy Or Post Partum, John J Byrne, Amir A Shamshirsaz, Alison G Cahill, Mark A Turrentine, Angela R Seasely, Joe Eid, Caroline E Rouse, Michael Richley, Nandini Raghuraman, Mariam Naqvi, Yasser Y El-Sayed, Martina L Badell, Cece Cheng, James Liu, Emily H Adhikari, Soha S Patel, Erika R O'Neil, Patrick S Ramsey

Faculty, Staff and Student Publications

IMPORTANCE: Existing reports of pregnant patients with COVID-19 disease who require extracorporeal membrane oxygenation (ECMO) are limited, with variable outcomes noted for the maternal-fetal dyad.

OBJECTIVE: To examine maternal and perinatal outcomes associated with ECMO used for COVID-19 with respiratory failure during pregnancy.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective multicenter cohort study examined pregnant and postpartum patients who required ECMO for COVID-19 respiratory failure at 25 hospitals across the US. Eligible patients included individuals who received care at one of the study sites, were diagnosed with SARS-CoV-2 infection during pregnancy or up to 6 weeks post partum by positive nucleic …

Prevalence And Descriptive Epidemiology Of Turner Syndrome In The United States, 2000-2017: A Report From The National Birth Defects Prevention Network, Bailey A Martin-Giacalone, Angela E Lin, Sonja A Rasmussen, Russell S Kirby, Eirini Nestoridi, Rebecca F Liberman, A J Agopian, John C Carey, Janet D Cragan, Nina Forestieri, Vinita Leedom, Aubree Boyce, Wendy N Nembhard, Monika Piccardi, Theresa Sandidge, Xiaoyi Shan, Charles J Shumate, Erin B Stallings, Roger Stevenson, Philip J Lupo

Faculty, Staff and Students Publications

The lack of United States population-based data on Turner syndrome limits assessments of prevalence and associated characteristics for this sex chromosome abnormality. Therefore, we collated 2000-2017 data from seven birth defects surveillance programs within the National Birth Defects Prevention Network. We estimated the prevalence of karyotype-confirmed Turner syndrome diagnosed within the first year of life. We also calculated the proportion of cases with commonly ascertained birth defects, assessed associations with maternal and infant characteristics using prevalence ratios (PR) with 95% confidence intervals (CI), and estimated survival probability. The prevalence of Turner syndrome of any pregnancy outcome was 3.2 per 10,000 …

Exploration Of Associations Among Dietary Tryptophan, Microbiome Composition And Function, And Symptom Severity In Irritable Bowel Syndrome, Anna M Plantinga, Kendra J Kamp, Qinglong Wu, Li Chen, Linda Yoo, Robert L Burr, Kevin C Cain, Daniel Raftery, Fausto Carnevale Neto, Shyam Badu, Sik Yu So, Tor Savidge, Robert J Shulman, Margaret M Heitkemper

Faculty, Staff and Students Publications

BACKGROUND: Imbalance of the tryptophan (TRP) pathway may influence symptoms among patients with irritable bowel syndrome (IBS). This study explored relationships among different components that contribute to TRP metabolism (dietary intake, stool metabolite levels, predicted microbiome metabolic capability) in females with IBS and healthy controls (HCs). Within the IBS group, we also investigated relationships between TRP metabolic determinants, Bifidobacterium abundance, and symptoms of IBS.

METHODS: Participants with IBS (Rome III) and HCs completed a 28-day diary of gastrointestinal symptoms and a 3-day food record for TRP intake. They provided a stool sample for shotgun metagenomics, 16 S rRNA analyses, and …

From Natchitoches To Nuremberg: The Life Of Legal Pioneer Lyria Dickason, Todd C. Peppers

Scholarly Articles

Lyria was one of a small handful of women who graduated from a Louisiana law school in the 1930’s. Despite the employment barriers facing female attorneys, she went on to become one of the first female law clerks in both the federal and state judiciary. To date, Lyria’s story has not been told. I have recently discovered, however, that Lyria’s children and grandchildren preserved her letters to her family. They are a treasure trove of information about a woman whose career took her from rural Louisiana to Louisiana’s highest court as well as the post-war ruins of Nazi Germany. The …

Zoster-Associated Prothrombotic Plasma Exosomes And Increased Stroke Risk, Andrew N Bubak, Christina Coughlan, Janelle Posey, Anthony J Saviola, Christy S Niemeyer, Serena W R Lewis, Sara Bustos Lopez, Adriana Solano, Stephen K Tyring, Cassidy Delaney, Keith B Neeves, Ravi Mahalingam, Kirk C Hansen, Maria A Nagel

Faculty, Staff and Student Publications

Herpes zoster (HZ; shingles) caused by varicella zoster virus reactivation increases stroke risk for up to 1 year after HZ. The underlying mechanisms are unclear, however, the development of stroke distant from the site of zoster (eg, thoracic, lumbar, sacral) that can occur months after resolution of rash points to a long-lasting, virus-induced soluble factor (or factors) that can trigger thrombosis and/or vasculitis. Herein, we investigated the content and contributions of circulating plasma exosomes from HZ and non-HZ patient samples. Compared with non-HZ exosomes, HZ exosomes (1) contained proteins conferring a prothrombotic state to recipient cells and (2) activated platelets …

Effect Of Angiotensin-Converting Enzyme Inhibitor And Angiotensin Receptor Blocker Initiation On Organ Support-Free Days In Patients Hospitalized With Covid-19: A Randomized Clinical Trial, Patrick R Lawler, Lennie P G Derde, Frank L Van De Veerdonk, Bryan J Mcverry, David T Huang, Lindsay R Berry, Elizabeth Lorenzi, Roland Van Kimmenade, Frank Gommans, Muthiah Vaduganathan, David E Leaf, Rebecca M Baron, Edy Y Kim, Claudia Frankfurter, Slava Epelman, Yvonne Kwan, Richard Grieve, Stephen O'Neill, Zia Sadique, Michael Puskarich, John C Marshall, Alisa M Higgins, Paul R Mouncey, Kathryn M Rowan, Farah Al-Beidh, Djillali Annane, Yaseen M Arabi, Carly Au, Abi Beane, Wilma Van Bentum-Puijk, Marc J M Bonten, Charlotte A Bradbury, Frank M Brunkhorst, Aidan Burrell, Adrian Buzgau, Meredith Buxton, Maurizio Cecconi, Allen C Cheng, Matthew Cove, Michelle A Detry, Lise J Estcourt, Justin Ezekowitz, Mark Fitzgerald, David Gattas, Lucas C Godoy, Herman Goossens, Rashan Haniffa, David A Harrison, Thomas Hills, Christopher M Horvat, Nao Ichihara, Francois Lamontagne, Kelsey M Linstrum, Daniel F Mcauley, Anna Mcglothlin, Shay P Mcguinness, Zoe Mcquilten, Srinivas Murthy, Alistair D Nichol, David R J Owen, Rachael L Parke, Jane C Parker, Katrina M Pollock, Luis Felipe Reyes, Hiroki Saito, Marlene S Santos, Christina T Saunders, Christopher W Seymour, Manu Shankar-Hari, Vanessa Singh, Alexis F Turgeon, Anne M Turner, Ryan Zarychanski, Cameron Green, Roger J Lewis, Derek C Angus, Scott Berry, Anthony C Gordon, Colin J Mcarthur, Steve A Webb

Faculty, Staff and Student Publications

IMPORTANCE: Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19.

OBJECTIVE: To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19.

DESIGN, SETTING, AND PARTICIPANTS: In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non-critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022).

INTERVENTIONS: Patients were randomized to receive open-label initiation of an ACE inhibitor …

Large-Scale Analysis Of Structural Brain Asymmetries In Schizophrenia Via The Enigma Consortium, Dick Schijven, Merel C Postema, Masaki Fukunaga, Junya Matsumoto, Kenichiro Miura, Sonja M C De Zwarte, Neeltje E M Van Haren, Wiepke Cahn, Hilleke E Hulshoff Pol, René S Kahn, Rosa Ayesa-Arriola, Víctor Ortiz-García De La Foz, Diana Tordesillas-Gutierrez, Javier Vázquez-Bourgon, Benedicto Crespo-Facorro, Dag Alnæs, Andreas Dahl, Lars T Westlye, Ingrid Agartz, Ole A Andreassen, Erik G Jönsson, Peter Kochunov, Jason M Bruggemann, Stanley V Catts, Patricia T Michie, Bryan J Mowry, Yann Quidé, Paul E Rasser, Ulrich Schall, Rodney J Scott, Vaughan J Carr, Melissa J Green, Frans A Henskens, Carmel M Loughland, Christos Pantelis, Cynthia Shannon Weickert, Thomas W Weickert, Lieuwe De Haan, Katharina Brosch, Julia-Katharina Pfarr, Kai G Ringwald, Frederike Stein, Andreas Jansen, Tilo T J Kircher, Igor Nenadić, Bernd Krämer, Oliver Gruber, Theodore D Satterthwaite, Juan Bustillo, Daniel H Mathalon, Adrian Preda, Vince D Calhoun, Judith M Ford, Steven G Potkin, Jingxu Chen, Yunlong Tan, Zhiren Wang, Hong Xiang, Fengmei Fan, Fabio Bernardoni, Stefan Ehrlich, Paola Fuentes-Claramonte, Maria Angeles Garcia-Leon, Amalia Guerrero-Pedraza, Raymond Salvador, Salvador Sarró, Edith Pomarol-Clotet, Valentina Ciullo, Fabrizio Piras, Daniela Vecchio, Nerisa Banaj, Gianfranco Spalletta, Stijn Michielse, Therese Van Amelsvoort, Erin W Dickie, Aristotle N Voineskos, Kang Sim, Simone Ciufolini, Paola Dazzan, Robin M Murray, Woo-Sung Kim, Young-Chul Chung, Christina Andreou, André Schmidt, Stefan Borgwardt, Andrew M Mcintosh, Heather C Whalley, Stephen M Lawrie, Stefan Du Plessis, Hilmar K Luckhoff, Freda Scheffler, Robin Emsley, Dominik Grotegerd, Rebekka Lencer, Udo Dannlowski, Jesse T Edmond, Kelly Rootes-Murdy, Julia M Stephen, Andrew R Mayer, Linda A Antonucci, Leonardo Fazio, Giulio Pergola, Alessandro Bertolino, Covadonga M Díaz-Caneja, Joost Janssen, Noemi G Lois, Celso Arango, Alexander S Tomyshev, Irina Lebedeva, Simon Cervenka, Carl M Sellgren, Foivos Georgiadis, Matthias Kirschner, Stefan Kaiser, Tomas Hajek, Antonin Skoch, Filip Spaniel, Minah Kim, Yoo Bin Kwak, Sanghoon Oh, Jun Soo Kwon, Anthony James, Geor Bakker, Christian Knöchel, Michael Stäblein, Viola Oertel, Anne Uhlmann, Fleur M Howells, Dan J Stein, Henk S Temmingh, Ana M Diaz-Zuluaga, Julian A Pineda-Zapata, Carlos López-Jaramillo, Stephanie Homan, Ellen Ji, Werner Surbeck, Philipp Homan, Simon E Fisher, Barbara Franke, David C Glahn, Ruben C Gur, Ryota Hashimoto, Neda Jahanshad, Eileen Luders, Sarah E Medland, Paul M Thompson, Jessica A Turner, Theo G M Van Erp, Clyde Francks

Faculty, Staff and Students Publications

Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small …

Lecanemab For Patients With Early Alzheimer Disease: Bayesian Analysis Of A Phase 2b Dose-Finding Randomized Clinical Trial, Donald A Berry, Shobha Dhadda, Michio Kanekiyo, David Li, Chad J Swanson, Michael Irizarry, Lynn D Kramer, Scott M Berry

Faculty, Staff and Student Publications

IMPORTANCE: Bayesian clinical trial designs are increasingly common; given their promotion by the US Food and Drug Administration, the future use of the bayesian approach will only continue to increase. Innovations possible when using the bayesian approach improve the efficiency of drug development and the accuracy of clinical trials, especially in the context of substantial data missingness.

OBJECTIVE: To explain the foundations, interpretations, and scientific justification of the bayesian approach in the setting of lecanemab trial 201, a bayesian-designed phase 2 dose-finding trial; to demonstrate the efficiency of using a bayesian design; and to show how it accommodates innovations in …

Age-Related Changes To Adipose Tissue And Peripheral Neuropathy In Genetically Diverse Het3 Mice Differ By Sex And Are Not Mitigated By Rapamycin Longevity Treatment., Jake W Willows, Morganne Robinson, Zahra Alshahal, Samantha K Morrison, Gargi Mishra, Harrison Cyr, Magdalena Blaszkiewicz, Gilian Gunsch, Sabrina Dipietro, Emma Paradie, Benjamin Tero, Anne Harrington, Larisa Ryzhova, Lucy Liaw, Peter C. Reifsnyder, David E Harrison, Kristy L Townsend

Faculty Research 2023

Neural communication between the brain and adipose tissues regulates energy expenditure and metabolism through modulation of adipose tissue functions. We have recently demonstrated that under pathophysiological conditions (obesity, diabetes, and aging), total subcutaneous white adipose tissue (scWAT) innervation is decreased ('adipose neuropathy'). With advanced age in the C57BL/6J mouse, small fiber peripheral nerve endings in adipose tissue die back, resulting in reduced contact with adipose-resident blood vessels and other cells. This vascular neuropathy and parenchymal neuropathy together likely pose a physiological challenge for tissue function. In the current work, we used the genetically diverse HET3 mouse model to investigate the …

Total Daily Energy Expenditure Has Declined Over The Past Three Decades Due To Declining Basal Expenditure, Not Reduced Activity Expenditure, John R Speakman, Jasper M A De Jong, Srishti Sinha, Klaas R Westerterp, Yosuke Yamada, Hiroyuki Sagayama, Philip N Ainslie, Liam J Anderson, Lenore Arab, Kweku Bedu-Addo, Stephane Blanc, Alberto G Bonomi, Pascal Bovet, Soren Brage, Maciej S Buchowski, Nancy F Butte, Stefan G J A Camps, Jamie A Cooper, Richard Cooper, Sai Krupa Das, Peter S W Davies, Lara R Dugas, Ulf Ekelund, Sonja Entringer, Terrence Forrester, Barry W Fudge, Melanie Gillingham, Santu Ghosh, Annelies H Goris, Michael Gurven, Lewis G Halsey, Catherine Hambly, Hinke H Haisma, Daniel Hoffman, Sumei Hu, Annemiek M Joosen, Jennifer L Kaplan, Peter Katzmarzyk, William E Kraus, Robert F Kushner, William R Leonard, Marie Löf, Corby K Martin, Eric Matsiko, Anine C Medin, Erwin P Meijer, Marian L Neuhouser, Theresa A Nicklas, Robert M Ojiambo, Kirsi H Pietiläinen, Jacob Plange-Rhule, Guy Plasqui, Ross L Prentice, Susan B Racette, David A Raichlen, Eric Ravussin, Leanne M Redman, Susan B Roberts, Michael C Rudolph, Luis B Sardinha, Albertine J Schuit, Analiza M Silva, Eric Stice, Samuel S Urlacher, Giulio Valenti, Ludo M Van Etten, Edgar A Van Mil, Brian M Wood, Jack A Yanovski, Tsukasa Yoshida, Xueying Zhang, Alexia J Murphy-Alford, Cornelia U Loechl, Anura Kurpad, Amy H Luke, Herman Pontzer, Matthew S Rodeheffer, Jennifer Rood, Dale A Schoeller, William W Wong

Faculty, Staff and Student Publications

Obesity is caused by prolonged positive energy balance1,2. Whether reduced energy expenditure stemming from reduced activity levels contributes, is debated3,4. Here we used the IAEA DLW database on energy expenditure of adults in the USA and Europe (n = 4799) to explore patterns in total (TEE: n=4799), basal (BEE: n = 1432) and physical activity energy expenditure (AEE: n = 1432) over time. In both sexes total energy expenditure (TEE) adjusted for body composition and age declined with time, while adjusted AEE increased over time. In males adjusted BEE decreased significantly, but …

Baseline Characteristics Of The North American Prodromal Synucleinopathy Cohort, Jonathan E Elliott, Jennifer Mcleland, Susan R Criswell, Yo-El S Ju, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Rapid eye movement (REM) sleep behavior disorder (RBD) is widely considered a prodromal synucleinopathy, as most with RBD develop overt synucleinopathy within ~10 years. Accordingly, RBD offers an opportunity to test potential treatments at the earliest stages of synucleinopathy. The North American Prodromal Synucleinopathy (NAPS) Consortium has created a multisite RBD participant, primarily clinic-based cohort to better understand characteristics at diagnosis, and in future work, identify predictors of phenoconversion, develop synucleinopathy biomarkers, and enable early stage clinical trial enrollment.

METHODS: Participants ≥18 years of age with overnight polysomnogram-confirmed RBD without Parkinson's disease, dementia, multiple system atrophy, or narcolepsy were …

Women In Sustainable Leadership: A Case Study On The Perspectives, Opportunities, And Challenges Of Biologist And Conservationist Estrela Matilde, Ella Lyons

Independent Study Project (ISP) Collection

Despite the relatively small population of 8,000 occupants and the minimal international recognition of the Island of Príncipe, located off of the Gulf of Guinea on the Western Coast of Central Africa, the region has increasingly become a leading example of sustainable practices to be taken on a global scale in the near future to combat our current climate crisis. This case study explores the sustainable practices that Príncipe has learned to embrace under the leadership of Portuguese conservation biologist and project manager for the NGO Fundação Príncipe, Estrela Matilde. Estrela integrates social, cultural, and environmental conservation to align with …

Generalized Joint Hypermobility And Lower Extremity Musculoskeletal Biomechanics In Female Athletes, Christopher F. Geiser

Dissertations (1934 -)

Generalized Joint Hypermobility (GJH), in lay terms being “double-jointed”, affects 5 to 43 percent of the general population. In severe forms, GJH impacts systems across the body, with cardiovascular, ocular, and musculoskeletal effects that can be quite debilitating. Most of the literature examining GJH is in this severely impacted group of people. However less severe forms of GJH are present in the athlete population in the same proportions, and athletes with GJH are more likely to be injured while participating in activities. They also experience greater time-loss injuries while participating in athletic activities. The movement biomechanics of those with severe …

Proteomic Predictors Of Incident Diabetes: Results From The Atherosclerosis Risk In Communities (Aric) Study, Mary R Rooney, Jingsha Chen, Justin B Echouffo-Tcheugui, Keenan A Walker, Pascal Schlosser, Aditya Surapaneni, Olive Tang, Jinyu Chen, Christie M Ballantyne, Eric Boerwinkle, Chiadi E Ndumele, Ryan T Demmer, James S Pankow, Pamela L Lutsey, Lynne E Wagenknecht, Yujian Liang, Xueling Sim, Rob Van Dam, E Shyong Tai, Morgan E Grams, Elizabeth Selvin, Josef Coresh

Faculty, Staff and Students Publications

Objective: The plasma proteome preceding diabetes can improve our understanding of diabetes pathogenesis.

Research design and methods: In 8,923 Atherosclerosis Risk in Communities (ARIC) Study participants (aged 47-70 years, 57% women, 19% Black), we conducted discovery and internal validation for associations of 4,955 plasma proteins with incident diabetes. We externally validated results in the Singapore Multi-Ethnic Cohort (MEC) nested case-control (624 case subjects, 1,214 control subjects). We used Cox regression to discover and validate protein associations and risk-prediction models (elastic net regression with cardiometabolic risk factors and proteins) for incident diabetes. We conducted a pathway analysis and examined causality using …

Naive T Cells Inhibit The Outgrowth Of Intractable Antigen-Activated Memory T Cells: Implications For T-Cell Immunotherapy, Sandhya Sharma, Mae Woods, Naren U Mehta, Tim Sauer, Kathan S Parikh, Michael Schmuck-Henneresse, Huimin Zhang, Birju Mehta, Malcolm K Brenner, Helen E Heslop, Cliona M Rooney

Faculty, Staff and Students Publications

BACKGROUND: The wider application of T cells targeting viral tumor-antigens via their native receptors is hampered by the failure to expand potent tumor-specific T cells from patients. Here, we examine reasons for and solutions to this failure, taking as our model the preparation of Epstein-Barr virus (EBV)-specific T cells (EBVSTs) for the treatment of EBV-positive lymphoma. EBVSTs could not be manufactured from almost one-third of patients, either because they failed to expand, or they expanded, but lacked EBV specificity. We identified an underlying cause of this problem and established a clinically feasible approach to overcome it.

METHODS: CD45RO+CD45RA- memory compartment …

Renal-Hepatic-Pancreatic Dysplasia Type 2: Perinatal Lethal Condition Or A Multisystemic Disorder With Variable Expressivity, Kathryn Gunther, Essam M Imseis, Joyce P Samuel, Elizabeth A Hillman, Tiina H Ojala, Timo Jahnukainen, Paul R Hillman

Faculty, Staff and Student Publications

BACKGROUND: Renal-hepatic-pancreatic dysplasia type 2 (RHPD2) is a rare condition that has been described in the literature disproportionately in perinatal losses. The main features of liver and kidney involvement are well described, with cardiac malformations and cardiomyopathy adding additional variation to the phenotype. Many patients reported are within larger cohorts of congenital anomalies of kidney and urinary tract (CAKUT) or liver failure, and with minimal phenotypic and clinical course data.

METHODS: An independent series of phenotypes and prognosis was aggregated from the literature. In this literature review, we describe an additional patient with RHPD2, provide a clinical update on the …

Ablative Margins Of Colorectal Liver Metastases Using Deformable Ct Image Registration And Autosegmentation, Yuan-Mao Lin, Iwan Paolucci, Caleb S O'Connor, Brian M Anderson, Bastien Rigaud, Bryan M Fellman, Kyle A Jones, Kristy K Brock, Bruno C Odisio

Faculty, Staff and Student Publications

Background

Confirming ablation completeness with sufficient ablative margin is critical for local tumor control following colorectal liver metastasis (CLM) ablation. An image-based confirmation method considering patient- and ablation-related biomechanical deformation is an unmet need.

Purpose

To evaluate a biomechanical deformable image registration (DIR) method for three-dimensional (3D) minimal ablative margin (MAM) quantification and the association with local disease progression following CT-guided CLM ablation.

Materials and Methods

This single-institution retrospective study included patients with CLM treated with CT-guided microwave or radiofrequency ablation from October 2015 to March 2020. A biomechanical DIR method with AI-based autosegmentation of liver, tumors, and ablation zones …

Evaluating The Causal Effect Of Tobacco Smoking On White Matter Brain Aging: A Two-Sample Mendelian Randomization Analysis In Uk Biobank, Chen Mo, Jingtao Wang, Zhenyao Ye, Hongjie Ke, Song Liu, Kathryn Hatch, Si Gao, Jessica Magidson, Chixiang Chen, Braxton D Mitchell, Peter Kochunov, L Elliot Hong, Tianzhou Ma, Shuo Chen

Faculty, Staff and Student Publications

BACKGROUND AND AIMS: Tobacco smoking is a risk factor for impaired brain function, but its causal effect on white matter brain aging remains unclear. This study aimed to measure the causal effect of tobacco smoking on white matter brain aging.

DESIGN: Mendelian randomization (MR) analysis using two non-overlapping data sets (with and without neuroimaging data) from UK Biobank (UKB). The group exposed to smoking and control group consisted of current smokers and never smokers, respectively. Our main method was generalized weighted linear regression with other methods also included as sensitivity analysis.

SETTING: United Kingdom.

PARTICIPANTS: The study cohort included 23 …

The Hyper-Incarceration Of Female Minority Juvenile Offenders Within The Juvenile And Criminal Justice Systems, Ruth C.A. Philippe

Selected Honors Theses

Young women are the fastest-growing portion of the juvenile justice system population. Girls experience risk factors at higher rates than boys, exhibit mental health issues at higher rates than boys, suffer more negative consequences from justice system involvement than system-involved boys, and are less likely to access treatment than boys. Girls are also more likely to become involved with the justice system for minor offenses such as running away or skipping school. In particular, young women of color receive unfair treatment than their counterparts. Girls of color are disadvantaged and treated differently within both the juvenile and criminal justice systems …

Renal-Hepatic-Pancreatic Dysplasia Type 2: Perinatal Lethal Condition Or A Multisystemic Disorder With Variable Expressivity, Kathryn Gunther, Essam M Imseis, Joyce P Samuel, Elizabeth A Hillman, Tiina H Ojala, Timo Jahnukainen, Paul R Hillman

Faculty, Staff and Student Publications

BACKGROUND: Renal-hepatic-pancreatic dysplasia type 2 (RHPD2) is a rare condition that has been described in the literature disproportionately in perinatal losses. The main features of liver and kidney involvement are well described, with cardiac malformations and cardiomyopathy adding additional variation to the phenotype. Many patients reported are within larger cohorts of congenital anomalies of kidney and urinary tract (CAKUT) or liver failure, and with minimal phenotypic and clinical course data.

METHODS: An independent series of phenotypes and prognosis was aggregated from the literature. In this literature review, we describe an additional patient with RHPD2, provide a clinical update on the …

Dietary Intake Of Total, Heme And Non-Heme Iron And The Risk Of Colorectal Cancer In A European Prospective Cohort Study, Elom K Aglago, Amanda J Cross, Elio Riboli, Veronika Fedirko, David J Hughes, Agnes Fournier, Paula Jakszyn, Heinz Freisling, Marc J Gunter, Christina C Dahm, Kim Overvad, Anne Tjønneland, Cecilie Kyrø, Marie-Christine Boutron-Ruault, Joseph A Rothwell, Gianluca Severi, Verena Katzke, Bernard Srour, Matthias B Schulze, Clemens Wittenbecher, Domenico Palli, Sabina Sieri, Fabrizio Pasanisi, Rosario Tumino, Fulvio Ricceri, Bas Bueno-De-Mesquita, Jeroen W G Derksen, Guri Skeie, Torill Enget Jensen, Marko Lukic, Maria-Jose Sánchez, Pilar Amiano, Sandra Colorado-Yohar, Aurelio Barricarte, Ulrika Ericson, Bethany Van Guelpen, Keren Papier, Anika Knuppel, Corinne Casagrande, Inge Huybrechts, Alicia K Heath, Konstantinos K Tsilidis, Mazda Jenab

Faculty, Staff and Student Publications

BACKGROUND: Iron is an essential micronutrient with differing intake patterns and metabolism between men and women. Epidemiologic evidence on the association of dietary iron and its heme and non-heme components with colorectal cancer (CRC) development is inconclusive.

METHODS: We examined baseline dietary questionnaire-assessed intakes of total, heme, and non-heme iron and CRC risk in the EPIC cohort. Sex-specific multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were computed using Cox regression. We modelled substitution of a 1 mg/day of heme iron intake with non-heme iron using the leave one-out method.

RESULTS: Of 450,105 participants (318,680 women) followed for 14.2 …

Incidence Rates Of Medically Attended Covid-19 In Infants Less Than 6 Months Of Age, Isabel Griffin, Stephanie A Irving, Carmen Sofia Arriola, Angela P Campbell, De-Kun Li, Fatimah S Dawood, Caroline Doughty-Skierski, Jeannette R Ferber, Nickolas Ferguson, Louise Hadden, Jillian T Henderson, Mary Juergens, Venkatesh Kancharla, Allison L Naleway, Gabriella Newes-Adeyi, Erin Nicholson, Roxana Odouli, Lawrence Reichle, Mo Sanyang, Kate Woodworth, Flor M Munoz

Faculty, Staff and Students Publications

BACKGROUND: Studies suggest infants may be at increased risk of severe coronavirus disease 2019 (COVID-19) relative to older children, but few data exist regarding the incidence of COVID-19 episodes and associated risk factors. We estimate incidence rates and describe characteristics associated with medically attended COVID-19 episodes among infants younger than 6 months of age.

METHODS: We analyzed electronic medical record data from a cohort of infants born March 1, 2020-February 28, 2021. Data from 3 health care delivery systems included demographic characteristics, maternal and infant outpatient visit and hospitalization diagnoses and severe acute respiratory syndrome coronavirus syndrome 2 (SARS-CoV-2) test …

Natural History Of Tango2 Deficiency Disorder: Baseline Assessment Of 73 Patients, Christina Y Miyake, Erica J Lay, Claudia Soler-Alfonso, Kevin E Glinton, Kimberly M Houck, Mustafa Tosur, Nancy E Moran, Sara B Stephens, Fernando Scaglia, Taylor S Howard, Jeffrey J Kim, Tam Dam Pham, Santiago O Valdes, Na Li, Chaya N Murali, Lilei Zhang, Maina Kava, Deane Yim, Cheyenne Beach, Gregory Webster, Leonardo Liberman, Christopher M Janson, Prince J Kannankeril, Samantha Baxter, Moriel Singer-Berk, Jordan Wood, Samuel J Mackenzie, Michael Sacher, Lina Ghaloul-Gonzalez, Claudia Pedroza, Shaine A Morris, Saad A Ehsan, Mahshid S Azamian, Seema R Lalani

Faculty, Staff and Students Publications

PURPOSE: TANGO2 deficiency disorder (TDD), an autosomal recessive disease first reported in 2016, is characterized by neurodevelopmental delay, seizures, intermittent ataxia, hypothyroidism, and life-threatening metabolic and cardiac crises. The purpose of this study was to define the natural history of TDD.

METHODS: Data were collected from an ongoing natural history study of patients with TDD enrolled between February 2019 and May 2022. Data were obtained through phone or video based parent interviews and medical record review.

RESULTS: Data were collected from 73 patients (59% male) from 57 unrelated families living in 16 different countries. The median age of participants at …

Probenecid Slows Disease Progression In A Murine Model Of Autosomal Dominant Polycystic Kidney Disease, Sergey N. Arkhipov, D'Anna L. Potter, Regina F. Sultanova, Daria V. Ilatovskaya, Peter C. Harris, Tengis S. Pavlov

Hypertension and Vascular Research Articles

Development of autosomal dominant polycystic kidney disease (ADPKD) involves renal epithelial cell abnormalities. Cystic fluid contains a high level of ATP that, among other effects, leads to a reduced reabsorption of electrolytes in cyst-lining cells, and thus results in cystic fluid accumulation. Earlier, we demonstrated that Pkd1(RC/RC) mice, a hypomorphic model of ADPKD, exhibit increased expression of pannexin-1, a membrane channel capable of ATP release. In the current study, we found that human ADPKD cystic epithelia have higher pannexin-1 abundance than normal collecting ducts. We hypothesized that inhibition of pannexin-1 function with probenecid can be used to attenuate ADPKD development. …

Pilot Clinical Trial Of Macimorelin To Assess Safety And Efficacy In Patients With Cancer Cachexia, Megan Herodes, Lindsey J Anderson, Samuel Shober, Ellen A Schur, Solomon A Graf, Nicola Ammer, Ramiro Salas, Marco Marcelli, Jose M Garcia

Faculty, Staff and Students Publications

BACKGROUND: Cancer cachexia is associated with reduced body weight, appetite and quality of life (QOL) with no approved treatments. Growth hormone secretagogues like macimorelin have potential to mitigate these effects.

METHODS: This pilot study assessed the safety and efficacy of macimorelin for 1 week. Efficacy was defined a priori as 1-week change in body weight (≥0.8 kg), plasma insulin-like growth factor (IGF)-1 (≥50 ng/mL) or QOL (≥15%). Secondary outcomes included food intake, appetite, functional performance, energy expenditure and safety laboratory parameters. Patients with cancer cachexia were randomized to 0.5 or 1.0 mg/kg macimorelin or placebo; outcomes were assessed non-parametrically.

RESULTS: …