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The Effect Of Including Benchmark Prevalence Data Of Common Imaging Findings In Spine Image Reports On Health Care Utilization Among Adults Undergoing Spine Imaging: A Stepped-Wedge Randomized Clinical Trial, Jeffrey G. Jarvik, Eric N. Meier, Kathryn T. James, Laura S. Gold, Katherine W. Tan, Larry G. Kessler, Pradeep Suri, David F. Kallmes, Daniel C. Cherkin, Richard A. Deyo, Karen J. Sherman, Safwan S. Halabi, Bryan A. Comstock, Patrick H. Luetmer, Andrew L. Avins, Sean D. Rundell, Brent Griffith, Janna L. Friedly, Danielle C. Lavallee, Kari A. Stephens, Judith A. Turner, Brian W. Bresnahan, Patrick J. Heagerty Sep 2020

The Effect Of Including Benchmark Prevalence Data Of Common Imaging Findings In Spine Image Reports On Health Care Utilization Among Adults Undergoing Spine Imaging: A Stepped-Wedge Randomized Clinical Trial, Jeffrey G. Jarvik, Eric N. Meier, Kathryn T. James, Laura S. Gold, Katherine W. Tan, Larry G. Kessler, Pradeep Suri, David F. Kallmes, Daniel C. Cherkin, Richard A. Deyo, Karen J. Sherman, Safwan S. Halabi, Bryan A. Comstock, Patrick H. Luetmer, Andrew L. Avins, Sean D. Rundell, Brent Griffith, Janna L. Friedly, Danielle C. Lavallee, Kari A. Stephens, Judith A. Turner, Brian W. Bresnahan, Patrick J. Heagerty

Diagnostic Radiology Articles

Importance: Lumbar spine imaging frequently reveals findings that may seem alarming but are likely unrelated to pain. Prior work has suggested that inserting data on the prevalence of imaging findings among asymptomatic individuals into spine imaging reports may reduce unnecessary subsequent interventions.

Objective: To evaluate the impact of including benchmark prevalence data in routine spinal imaging reports on subsequent spine-related health care utilization and opioid prescriptions.

Design, Setting, and Participants: This stepped-wedge, pragmatic randomized clinical trial included 250 401 adult participants receiving care from 98 primary care clinics at 4 large health systems in the United States. Participants had imaging …


Impact Of Annual And Semi-Annual Mass Drug Administration For Lymphatic Filariasis And Onchocerciasis On Hookworm Infection In Côte D'Ivoire, Agodio Loukouri, Aboulaye Méité, Benjamin G. Koudou, Charles W. Goss, Daphne Lew, Gary J. Weil, Eliezer K. N'Goran, Peter U. Fischer Sep 2020

Impact Of Annual And Semi-Annual Mass Drug Administration For Lymphatic Filariasis And Onchocerciasis On Hookworm Infection In Côte D'Ivoire, Agodio Loukouri, Aboulaye Méité, Benjamin G. Koudou, Charles W. Goss, Daphne Lew, Gary J. Weil, Eliezer K. N'Goran, Peter U. Fischer

Open Access Publications

Mass Drug Administration (MDA) programs to eliminate Lymphatic Filariasis (LF) in western Africa use the anthelminthics ivermectin plus albendazole. These drugs have the potential to impact also Soil-Transmitted Helminth (STH) infections, since the drugs have a broad range of anthelminthic activity. Integration of preventive chemotherapy efforts for LF, onchocerciasis and STH is recommended by the World Health Organization (WHO) in order to avoid duplication of MDA and to reduce costs. The objective of the current study was to determine whether five semi-annual rounds of community-wide MDA to eliminate LF and onchocerciasis have a greater impact on STH than three annual …


Masculinized Second-To-Fourth Digit Ratio (2d:4d Ratio) Is Associated With Lower Cortisol Response In Infant Female Rhesus Monkeys (Macaca Mulatta), Elizabeth K. Wood, Parker Jarman, Elysha Cash, Alexander Baxter, John P. Capitanio, James Dee Higley Sep 2020

Masculinized Second-To-Fourth Digit Ratio (2d:4d Ratio) Is Associated With Lower Cortisol Response In Infant Female Rhesus Monkeys (Macaca Mulatta), Elizabeth K. Wood, Parker Jarman, Elysha Cash, Alexander Baxter, John P. Capitanio, James Dee Higley

Faculty Publications

The second-to-fourth digit ratio (2D:4D ratio) is considered a postnatal proxy measure for the degree of prenatal androgen exposure (PAE), which is the primary factor responsible for masculinizing the brain of a developing fetus. Some studies suggest that the organizational effects of PAE may extend to the hypothalamic-pituitary-adrenal (HPA) axis response to stress. This study investigates the relationship between 2D:4D ratio and HPA axis functioning using a rhesus monkey (Macaca mulatta) model. Subjects were N = 268 (180 females, 88 males) rhesus monkey infants (3–4 months of age). Plasma cortisol concentrations were assayed from two blood samples obtained …


Self-Regulation And Emotional Reactivity In Infants With Prenatal Exposure To Opioids And Alcohol, Kathryn G Beauchamp, Jean Lowe, Ronald M Schrader, Shikhar Shrestha, Crystal Aragón, Natalia Moss, Julia M Stephen, Ludmila N Bakhireva Sep 2020

Self-Regulation And Emotional Reactivity In Infants With Prenatal Exposure To Opioids And Alcohol, Kathryn G Beauchamp, Jean Lowe, Ronald M Schrader, Shikhar Shrestha, Crystal Aragón, Natalia Moss, Julia M Stephen, Ludmila N Bakhireva

Pediatrics Research and Scholarship

BACKGROUND: Infants with prenatal substance exposure are at increased risk for developmental problems, with self-regulatory challenges being some of the most pronounced. The current study aimed to investigate the extent to which prenatal substance exposure (alcohol, opioids) impacts infant self-regulation during a relational stressor and the association between self-regulation and infant affect.

METHODS: Participants were 100 mother-child dyads recruited prenatally (Mean = 23.8 gestational weeks) and completed the Still Face Paradigm (SFP) when infants were 5 to 8 months of age (Mean = 6.9 months) as part of an ENRICH prospective birth cohort study. Based on prospective repeated assessment of …


Covid-19: Postmortem Diagnostic And Biosafety Considerations, J Matthew Lacy, Erin G. Brooks, Joshua Akers, Danielle Armstrong, Lauren Decker, Adam Gonzalez, William Humphrey, Romana Mayer, Matthew Miller, Catherine Perez, Jose Antonio Ruiz Arango, Lakshmanan Sathyavagiswaran, Wendy Stroh, Suzanne Utley Sep 2020

Covid-19: Postmortem Diagnostic And Biosafety Considerations, J Matthew Lacy, Erin G. Brooks, Joshua Akers, Danielle Armstrong, Lauren Decker, Adam Gonzalez, William Humphrey, Romana Mayer, Matthew Miller, Catherine Perez, Jose Antonio Ruiz Arango, Lakshmanan Sathyavagiswaran, Wendy Stroh, Suzanne Utley

Pathology Research and Scholarship

As a result of the 2019 novel human coronavirus (COVID-19) global spread, medical examiner/coroner offices will inevitably encounter increased numbers of COVID-19-infected decedents at autopsy. While in some cases a history of fever and/or respiratory distress (eg, cough or shortness of breath) may suggest the diagnosis, epidemiologic studies indicate that the majority of individuals infected with COVID-19 develop mild to no symptoms. Those dying with-but not of-COVID-19 may still be infectious, however. While multiple guidelines have been issued regarding autopsy protocol in cases of suspected COVID-19 deaths, there is some variability in the recommendations. Additionally, limited recommendations to date have …


Postmortem Computed Tomography In Firearm Homicides: A Retrospective Case Series, Marloes E M Vester, Kurt B Nolte, Gary M. Hatch, Chandra Y. Gerrard, Reinoud D. Stoel, Rick R. Van Rijn Sep 2020

Postmortem Computed Tomography In Firearm Homicides: A Retrospective Case Series, Marloes E M Vester, Kurt B Nolte, Gary M. Hatch, Chandra Y. Gerrard, Reinoud D. Stoel, Rick R. Van Rijn

Pathology Research and Scholarship

Postmortem computed tomography (PMCT) is integrated into the evaluation of decedents in several American medical examiner offices and medicolegal death investigative centers in many other countries. We retrospectively investigated the value of PMCT in a series of firearm homicide cases from a statewide centralized medical examiner's office that occurred during 2016. Autopsies were performed or supervised by board-certified forensic pathologists who reviewed the PMCT scans prior to autopsy. PMCT scans were re-evaluated by a forensic radiologist blinded to the autopsy findings and scored by body region (head-neck, thoracoabdominal, and extremities). Injury discrepancies were scored using a modified Goldman classification and …


Minimizing Surgical Blood Loss At Cesarean Hysterectomy For Placenta Previa With Evidence Of Placenta Increta Or Placenta Percreta: The State Of Play In 2020, John C. Kingdom, Sebastian R. Hobson, Ally Murji, Lisa Allen, Rory C. Windrim, Evelyn Lockhart, Sally L. Collins, Hooman Soleymani Majd, Moiad Alazzam, Feras Naaisa, Alireza A. Shamshirsaz, Michael A. Belfort, Karin A. Fox Sep 2020

Minimizing Surgical Blood Loss At Cesarean Hysterectomy For Placenta Previa With Evidence Of Placenta Increta Or Placenta Percreta: The State Of Play In 2020, John C. Kingdom, Sebastian R. Hobson, Ally Murji, Lisa Allen, Rory C. Windrim, Evelyn Lockhart, Sally L. Collins, Hooman Soleymani Majd, Moiad Alazzam, Feras Naaisa, Alireza A. Shamshirsaz, Michael A. Belfort, Karin A. Fox

Pathology Research and Scholarship

The evolution of multidisciplinary team-based care for women with placenta accreta spectrum disorder has delivered stepwise improvements in clinical outcomes. Central to this overall goal is the ability to limit blood loss at surgery. Placement of inflatable balloons within the pelvic arteries, most commonly in the anterior divisions of the internal iliac arteries, became popular in many centers, at the expense of prolonging surgical care and with attendant risks of vascular injury. In tandem, the need to expose pelvic sidewall anatomy to safely identify the course of the ureters re-popularized the alternative strategy of ligating the same anterior divisions of …


Combinatorial Pharmacogenomic Testing Improves Outcomes For Older Adults With Depression, Brent P Forester, Charles R Conway, Et Al Sep 2020

Combinatorial Pharmacogenomic Testing Improves Outcomes For Older Adults With Depression, Brent P Forester, Charles R Conway, Et Al

2020-Current year OA Pubs

OBJECTIVE: Evaluate the clinical utility of combinatorial pharmacogenomic testing for informing medication selection among older adults who have experienced antidepressant medication failure for major depressive disorder (MDD).

DESIGN: Post hoc analysis of data from a blinded, randomized controlled trial comparing two active treatment arms.

SETTING: Psychiatry specialty and primary care clinics across 60 U.S. community and academic sites.

PARTICIPANTS: Adults age 65 years or older at baseline (n = 206), diagnosed with MDD and inadequate response to at least one medication on the combinatorial pharmacogenomic test report during the current depressive episode.

INTERVENTION: Combinatorial pharmacogenomic testing to inform medication selection …


Nine-Year Prospective Efficacy And Safety Of Brain-Responsive Neurostimulation For Focal Epilepsy, Dileep R Nair, Kenneth D Laxer, Peter B Weber, Anthony M Murro, Yong D Park, Gregory L Barkley, Brien J Smith, Ryder P Gwinn, Michael J Doherty, Katherine H Noe, Richard S Zimmerman, Gregory K Bergey, William S Anderson, Christianne Heck, Charles Y Liu, Ricky W Lee, Toni Sadler, Robert B Duckrow, Lawrence J Hirsch, Robert E Wharen, William Tatum, Shraddha Srinivasan, Guy M Mckhann, Mark A Agostini, Andreas V Alexopoulos, Barbara C Jobst, David W Roberts, Vicenta Salanova, Thomas C Witt, Sydney S Cash, Andrew J Cole, Gregory A Worrell, Brian N Lundstrom, Jonathan C Edwards, Jonathan J Halford, David C Spencer, Lia Ernst, Christopher T Skidmore, Michael R Sperling, Ian Miller, Eric B Geller, Michel J Berg, A James Fessler, Paul Rutecki, Alica M Goldman, Eli M Mizrahi, Robert E Gross, Donald C Shields, Theodore H Schwartz, Douglas R Labar, Nathan B Fountain, W Jeff Elias, Piotr W Olejniczak, Nicole R Villemarette-Pittman, Stephan Eisenschenk, Steven N Roper, Jane G Boggs, Tracy A Courtney, Felice T Sun, Cairn G Seale, Kathy L Miller, Tara L Skarpaas, Martha J Morrell, Rns System Ltt Study Sep 2020

Nine-Year Prospective Efficacy And Safety Of Brain-Responsive Neurostimulation For Focal Epilepsy, Dileep R Nair, Kenneth D Laxer, Peter B Weber, Anthony M Murro, Yong D Park, Gregory L Barkley, Brien J Smith, Ryder P Gwinn, Michael J Doherty, Katherine H Noe, Richard S Zimmerman, Gregory K Bergey, William S Anderson, Christianne Heck, Charles Y Liu, Ricky W Lee, Toni Sadler, Robert B Duckrow, Lawrence J Hirsch, Robert E Wharen, William Tatum, Shraddha Srinivasan, Guy M Mckhann, Mark A Agostini, Andreas V Alexopoulos, Barbara C Jobst, David W Roberts, Vicenta Salanova, Thomas C Witt, Sydney S Cash, Andrew J Cole, Gregory A Worrell, Brian N Lundstrom, Jonathan C Edwards, Jonathan J Halford, David C Spencer, Lia Ernst, Christopher T Skidmore, Michael R Sperling, Ian Miller, Eric B Geller, Michel J Berg, A James Fessler, Paul Rutecki, Alica M Goldman, Eli M Mizrahi, Robert E Gross, Donald C Shields, Theodore H Schwartz, Douglas R Labar, Nathan B Fountain, W Jeff Elias, Piotr W Olejniczak, Nicole R Villemarette-Pittman, Stephan Eisenschenk, Steven N Roper, Jane G Boggs, Tracy A Courtney, Felice T Sun, Cairn G Seale, Kathy L Miller, Tara L Skarpaas, Martha J Morrell, Rns System Ltt Study

Faculty, Staff and Students Publications

OBJECTIVE: To prospectively evaluate safety and efficacy of brain-responsive neurostimulation in adults with medically intractable focal onset seizures (FOS) over 9 years.

METHODS: Adults treated with brain-responsive neurostimulation in 2-year feasibility or randomized controlled trials were enrolled in a long-term prospective open label trial (LTT) to assess safety, efficacy, and quality of life (QOL) over an additional 7 years. Safety was assessed as adverse events (AEs), efficacy as median percent change in seizure frequency and responder rate, and QOL with the Quality of Life in Epilepsy (QOLIE-89) inventory.

RESULTS: Of 256 patients treated in the initial trials, 230 participated in …


Impact Of Investigational Microbiota Therapeutic Rbx2660 On The Gut Microbiome And Resistome Revealed By A Placebo-Controlled Clinical Trial, Suryang Kwak, Joohee Choi, Tiffany Hink, Kimberly A Reske, Kenneth Blount, Courtney Jones, Margaret H Bost, Xiaoqing Sun, Carey-Ann D Burnham, Erik R Dubberke, Gautam Dantas, Cdc Prevention Epicenter Program Aug 2020

Impact Of Investigational Microbiota Therapeutic Rbx2660 On The Gut Microbiome And Resistome Revealed By A Placebo-Controlled Clinical Trial, Suryang Kwak, Joohee Choi, Tiffany Hink, Kimberly A Reske, Kenneth Blount, Courtney Jones, Margaret H Bost, Xiaoqing Sun, Carey-Ann D Burnham, Erik R Dubberke, Gautam Dantas, Cdc Prevention Epicenter Program

2020-Current year OA Pubs

BACKGROUND: Intestinal microbiota restoration can be achieved by complementing a subject's perturbed microbiota with that of a healthy donor. Recurrent Clostridioides difficile infection (rCDI) is one key application of such treatment. Another emerging application of interest is reducing antibiotic-resistant genes (ARGs) and organisms (AROs). In this study, we investigated fecal specimens from a multicenter, randomized, double-blind, placebo-controlled phase 2b study of microbiota-based investigational drug RBX2660. Patients were administered either placebo, 1 dose of RBX2660 and 1 placebo, or 2 doses of RBX2660 via enema and longitudinally tracked for changes in their microbiome and antibiotic resistome.

RESULTS: All patients exhibited significant …


Regional Correlation Of Biochemical Measures Of Amyloid And Tau Phosphorylation In The Brain, Kanta Horie, Nicolas R Barthélemy, Nipun Mallipeddi, Yan Li, Erin E Franklin, Richard J Perrin, Randall J Bateman, Chihiro Sato Aug 2020

Regional Correlation Of Biochemical Measures Of Amyloid And Tau Phosphorylation In The Brain, Kanta Horie, Nicolas R Barthélemy, Nipun Mallipeddi, Yan Li, Erin E Franklin, Richard J Perrin, Randall J Bateman, Chihiro Sato

2020-Current year OA Pubs

Alzheimer's disease (AD) neuropathologic change is characterized by amyloid plaques and neurofibrillary tangles (NFTs) that consist of aggregated amyloid beta (Abeta) and hyperphosphorylated tau proteins (p-tau), respectively. Although the global relationship between Abeta and p-tau has been studied for decades, it is still unclear whether a regional correlation exists between Abeta and p-tau in the human brain. Recent studies in cerebrospinal fluid (CSF) have suggested that tau phosphorylation at specific sites such as T217 is modified at an early stage of AD when amyloid plaques become detectable. We applied biochemical and mass spectrometry methods in human brain samples with and …


Genetic Variants And Functional Pathways Associated With Resilience To Alzheimer's Disease, Logan Dumitrescu, Carlos Cruchaga, Et Al Aug 2020

Genetic Variants And Functional Pathways Associated With Resilience To Alzheimer's Disease, Logan Dumitrescu, Carlos Cruchaga, Et Al

Open Access Publications

Approximately 30% of older adults exhibit the neuropathological features of Alzheimer's disease without signs of cognitive impairment. Yet, little is known about the genetic factors that allow these potentially resilient individuals to remain cognitively unimpaired in the face of substantial neuropathology. We performed a large, genome-wide association study (GWAS) of two previously validated metrics of cognitive resilience quantified using a latent variable modelling approach and representing better-than-predicted cognitive performance for a given level of neuropathology. Data were harmonized across 5108 participants from a clinical trial of Alzheimer's disease and three longitudinal cohort studies of cognitive ageing. All analyses were run …


Long Term Survival And Local Control Outcomes From Single Dose Targeted Intraoperative Radiotherapy During Lumpectomy (Targit-Iort) For Early Breast Cancer: Targit-A Randomised Clinical Trial., Jayant S Vaidya, Max Bulsara, Michael Baum, Frederik Wenz, Samuele Massarut, Steffi Pigorsch, Michael Alvarado, Michael Douek, Christobel Saunders, Henrik L Flyger, Wolfgang Eiermann, Chris Brew-Graves, Norman R Williams, Ingrid Potyka, Nicholas Roberts, Marcelle Bernstein, Douglas Brown, Elena Sperk, Siobhan Laws, Marc Sütterlin, Tammy Corica, Steinar Lundgren, Dennis R Holmes, Lorenzo Vinante, Fernando Bozza, Montserrat Pazos, Magali Le Blanc-Onfroy, Günther Gruber, Wojciech Polkowski, Konstantin J Dedes, Marcus Niewald, Jens Blohmer, David Mccready, Richard Hoefer, Pond Kelemen, Gloria Petralia, Mary Falzon, David J Joseph, Jeffrey S Tobias Aug 2020

Long Term Survival And Local Control Outcomes From Single Dose Targeted Intraoperative Radiotherapy During Lumpectomy (Targit-Iort) For Early Breast Cancer: Targit-A Randomised Clinical Trial., Jayant S Vaidya, Max Bulsara, Michael Baum, Frederik Wenz, Samuele Massarut, Steffi Pigorsch, Michael Alvarado, Michael Douek, Christobel Saunders, Henrik L Flyger, Wolfgang Eiermann, Chris Brew-Graves, Norman R Williams, Ingrid Potyka, Nicholas Roberts, Marcelle Bernstein, Douglas Brown, Elena Sperk, Siobhan Laws, Marc Sütterlin, Tammy Corica, Steinar Lundgren, Dennis R Holmes, Lorenzo Vinante, Fernando Bozza, Montserrat Pazos, Magali Le Blanc-Onfroy, Günther Gruber, Wojciech Polkowski, Konstantin J Dedes, Marcus Niewald, Jens Blohmer, David Mccready, Richard Hoefer, Pond Kelemen, Gloria Petralia, Mary Falzon, David J Joseph, Jeffrey S Tobias

Articles, Abstracts, and Reports

OBJECTIVE: To determine whether risk adapted intraoperative radiotherapy, delivered as a single dose during lumpectomy, can effectively replace postoperative whole breast external beam radiotherapy for early breast cancer.

DESIGN: Prospective, open label, randomised controlled clinical trial.

SETTING: 32 centres in 10 countries in the United Kingdom, Europe, Australia, the United States, and Canada.

PARTICIPANTS: 2298 women aged 45 years and older with invasive ductal carcinoma up to 3.5 cm in size, cN0-N1, eligible for breast conservation and randomised before lumpectomy (1:1 ratio, blocks stratified by centre) to either risk adapted targeted intraoperative radiotherapy (TARGIT-IORT) or external beam radiotherapy (EBRT).

INTERVENTIONS: …


Removal Of High Frequency Contamination From Motion Estimates In Single-Band Fmri Saves Data Without Biasing Functional Connectivity, Caterina Gratton, Ally Dworetsky, Rebecca S Coalson, Babatunde Adeyemo, Timothy O Laumann, Deanna M Barch, Nico U F Dosenbach, Abraham Z Snyder, Joel S Perlmutter, Steven E Petersen, Meghan C Campbell, Et Al. Aug 2020

Removal Of High Frequency Contamination From Motion Estimates In Single-Band Fmri Saves Data Without Biasing Functional Connectivity, Caterina Gratton, Ally Dworetsky, Rebecca S Coalson, Babatunde Adeyemo, Timothy O Laumann, Deanna M Barch, Nico U F Dosenbach, Abraham Z Snyder, Joel S Perlmutter, Steven E Petersen, Meghan C Campbell, Et Al.

2020-Current year OA Pubs

Denoising fMRI data requires assessment of frame-to-frame head motion and removal of the biases motion introduces. This is usually done through analysis of the parameters calculated during retrospective head motion correction (i.e., 'motion' parameters). However, it is increasingly recognized that respiration introduces factitious head motion via perturbations of the main (B0) field. This effect appears as higher-frequency fluctuations in the motion parameters (>0.1 ​Hz, here referred to as 'HF-motion'), primarily in the phase-encoding direction. This periodicity can sometimes be obscured in standard single-band fMRI (TR 2.0-2.5 ​s) due to aliasing. Here we examined (1) how prevalent HF-motion effects are …


Perceptions Of Self-Efficacy, Career Readiness, And Persistence By Female College Of Business Graduates Who Participated In A Formal Mentoring Program, Erika Krennerich Chudy Aug 2020

Perceptions Of Self-Efficacy, Career Readiness, And Persistence By Female College Of Business Graduates Who Participated In A Formal Mentoring Program, Erika Krennerich Chudy

Student Theses and Dissertations

This phenomenological study highlighted the perceptions of female college graduates toward self-efficacy, career readiness, and persistence, having participated in a formal mentoring program at a public four-year university. The purpose of this study was to gain insights into the beliefs, attitudes, and perceptions of the mentees toward the mentoring program. The sample interviewed for this study was female college graduates who experienced the mentoring program. Using a phenomenological approach, each graduate participated in an in-depth interview, and the researcher transcribed, coded, and synthesized the interviews to understand the shared experiences of the graduates. Some four-year public universities are struggling to …


Comparison Of Repeated Doses Of Ivermectin Versus Ivermectin Plus Albendazole For The Treatment Of Onchocerciasis: A Randomized, Open-Label, Clinical Trial, Linda Batsa Debrah, Kerstin Fischer, Gary Weil, Et Al. Aug 2020

Comparison Of Repeated Doses Of Ivermectin Versus Ivermectin Plus Albendazole For The Treatment Of Onchocerciasis: A Randomized, Open-Label, Clinical Trial, Linda Batsa Debrah, Kerstin Fischer, Gary Weil, Et Al.

2020-Current year OA Pubs

BACKGROUND: Improved treatment for onchocerciasis is needed to accelerate onchocerciasis elimination in Africa. Aiming to better exploit registered drugs, this study was undertaken to determine whether annual or semiannual treatment with ivermectin (IVM; 200 µg/kg) plus albendazole (ALB; 800 mg single dose) is superior to IVM alone.

METHODS: This trial was performed in Ghana and included 272 participants with microfilariae (MF), who were randomly assigned to 4 treatment arms: (1) IVM annually at 0, 12, and 24 months; (2) IVM semiannually at 0, 6, 12, 18, and 24 months; (3) IVM+ALB annually; or (4) IVM+ALB semiannually. Microfiladermia was determined pretreatment …


Gut Microbiota Features Associated With Campylobacter Burden And Postnatal Linear Growth Deficits In A Peruvian Birth Cohort, Saba Rouhani, Nicholas W Griffin, Pablo Peñataro Yori, Maribel Paredes Olortegui, Mery Siguas Salas, Dixner Rengifo Trigoso, Lawrence H Moulton, Eric R Houpt, Michael J Barratt, Margaret N Kosek, Jeffrey I Gordon Aug 2020

Gut Microbiota Features Associated With Campylobacter Burden And Postnatal Linear Growth Deficits In A Peruvian Birth Cohort, Saba Rouhani, Nicholas W Griffin, Pablo Peñataro Yori, Maribel Paredes Olortegui, Mery Siguas Salas, Dixner Rengifo Trigoso, Lawrence H Moulton, Eric R Houpt, Michael J Barratt, Margaret N Kosek, Jeffrey I Gordon

2020-Current year OA Pubs

BACKGROUND: Campylobacter infection is associated with impaired growth of children, even in the absence of symptoms. To examine the underlying mechanisms, we evaluated associations between Campylobacter infection, linear growth, and fecal microbial community features in a prospective birth cohort of 271 children with a high burden of diarrhea and stunting in the Amazonian lowlands of Peru.

METHODS: Campylobacter was identified using a broadly reactive, genus-specific enzyme-linked immunosorbent assay. 16S rRNA-based analyses were used to identify bacterial taxa in fecal samples at ages 6, 12, 18, and 24 months (N = 928). Associations between infection, growth, and gut microbial community composition …


Auxora Versus Standard Of Care For The Treatment Of Severe Or Critical Covid-19 Pneumonia: Results From A Randomized Controlled Trial, Joseph B. Miller Md, Charles Bruen, Michael Schnaus, Jeffrey Zhang, Sadia Ali, April Lind, Zachary Stoecker, Kenneth Stauderman, Sudarshan Hebbar Aug 2020

Auxora Versus Standard Of Care For The Treatment Of Severe Or Critical Covid-19 Pneumonia: Results From A Randomized Controlled Trial, Joseph B. Miller Md, Charles Bruen, Michael Schnaus, Jeffrey Zhang, Sadia Ali, April Lind, Zachary Stoecker, Kenneth Stauderman, Sudarshan Hebbar

Emergency Medicine Articles

BACKGROUND: Calcium release-activated calcium (CRAC) channel inhibitors stabilize the pulmonary endothelium and block proinflammatory cytokine release, potentially mitigating respiratory complications observed in patients with COVID-19. This study aimed to investigate the safety and efficacy of Auxora, a novel, intravenously administered CRAC channel inhibitor, in adults with severe or critical COVID-19 pneumonia.

METHODS: A randomized, controlled, open-label study of Auxora was conducted in adults with severe or critical COVID-19 pneumonia. Patients were randomized 2:1 to receive three doses of once-daily Auxora versus standard of care (SOC) alone. The primary objective was to assess the safety and tolerability of Auxora. Following FDA …


Adjunctive Testing By Cytology, P16/Ki-67 Dual-Stained Cytology Or Hpv16/18 E6 Oncoprotein For The Management Of Hpv16/18 Screen-Positive Women, Leticia Torres-Ibarra, Attila T. Lorincz, Cosette M. Wheeler, Jack Cuzick, Rubí Hernández-López, Donna Spiegelman, Leith León-Maldonado, Berenice Rivera-Paredez, Pablo Méndez-Hernández, Eduardo Lazcano-Ponce, Jorge Salmerón Aug 2020

Adjunctive Testing By Cytology, P16/Ki-67 Dual-Stained Cytology Or Hpv16/18 E6 Oncoprotein For The Management Of Hpv16/18 Screen-Positive Women, Leticia Torres-Ibarra, Attila T. Lorincz, Cosette M. Wheeler, Jack Cuzick, Rubí Hernández-López, Donna Spiegelman, Leith León-Maldonado, Berenice Rivera-Paredez, Pablo Méndez-Hernández, Eduardo Lazcano-Ponce, Jorge Salmerón

Pathology Research and Scholarship

High-risk human papillomavirus type 16/18 (HPV16/18) genotyping is unable to accurately discriminate nonprogressive infections from those that will progress to cervical cancer. Our study aimed to assesses if additional testing either with liquid-based cytology (LBC) or the putative progression markers p16/Ki-67 and HPV16/18 E6 oncoprotein (E6) can improve the efficiency of HPV16/18 genotyping for triaging high-risk HPV (hrHPV)-positive women through better cancer risk stratification. Women attending colposcopy after positive HPV16/18 genotyping results within the Forwarding Research for Improved Detection and Access for Cervical Cancer Screening and Triage (FRIDA) hrHPV-based screening study in Tlaxcala, Mexico, underwent further testing with LBC, p16/Ki-67 …


Testing The Impact Of A Single Nucleotide Polymorphism In A Plasmodium Berghei Apiap2 Transcription Factor On Experimental Cerebral Malaria In Mice, Munir Akkaya, Abhisheka Bansal, Patrick W Sheehan, Mirna Pena, Clare K Cimperman, Chen Feng Qi, Takele Yazew, Thomas D Otto, Oliver Billker, Louis H Miller, Susan K Pierce Aug 2020

Testing The Impact Of A Single Nucleotide Polymorphism In A Plasmodium Berghei Apiap2 Transcription Factor On Experimental Cerebral Malaria In Mice, Munir Akkaya, Abhisheka Bansal, Patrick W Sheehan, Mirna Pena, Clare K Cimperman, Chen Feng Qi, Takele Yazew, Thomas D Otto, Oliver Billker, Louis H Miller, Susan K Pierce

Open Access Publications

Cerebral malaria (CM) is the deadliest form of severe Plasmodium infections. Currently, we have limited understanding of the mechanisms by which Plasmodium parasites induce CM. The mouse model of CM, experimental CM (ECM), induced by infection with the rodent parasite, Plasmodium berghei ANKA (PbANKA) has been extensively used to study the pathophysiology of CM. Recent genomic analyses revealed that the coding regions of PbANKA and the closely related Plasmodium berghei NK65 (PbNK65), that does not cause ECM, differ in only 21 single nucleotide polymorphysims (SNPs). Thus, the SNP-containing genes might contribute to the pathogenesis of ECM. Although the majority of …


De Novo And Bi-Allelic Pathogenic Variants In Nars1 Cause Neurodevelopmental Delay Due To Toxic Gain-Of-Function And Partial Loss-Of-Function Effects, Andreea Manole, Marwan Shinawi, Marisa V. Andrews, Dustin Baldridge, John F. Mantovani, Et Al. Aug 2020

De Novo And Bi-Allelic Pathogenic Variants In Nars1 Cause Neurodevelopmental Delay Due To Toxic Gain-Of-Function And Partial Loss-Of-Function Effects, Andreea Manole, Marwan Shinawi, Marisa V. Andrews, Dustin Baldridge, John F. Mantovani, Et Al.

2020-Current year OA Pubs

Aminoacyl-tRNA synthetases (ARSs) are ubiquitous, ancient enzymes that charge amino acids to cognate tRNA molecules, the essential first step of protein translation. Here, we describe 32 individuals from 21 families, presenting with microcephaly, neurodevelopmental delay, seizures, peripheral neuropathy, and ataxia, with de novo heterozygous and bi-allelic mutations in asparaginyl-tRNA synthetase (NARS1). We demonstrate a reduction in NARS1 mRNA expression as well as in NARS1 enzyme levels and activity in both individual fibroblasts and induced neural progenitor cells (iNPCs). Molecular modeling of the recessive c.1633C>T (p.Arg545Cys) variant shows weaker spatial positioning and tRNA selectivity. We conclude that de novo and …


Oral Cancer: Clinicopathological Features And Associated Risk Factors In A High Risk Population Presenting To A Major Tertiary Care Center In Pakistan, Namrah Anwar, Shahid Pervez, Qurratulain Chundriger, Mohammad Sohail Awan, Tariq Moatter, Tazeen Saeed Ali Aug 2020

Oral Cancer: Clinicopathological Features And Associated Risk Factors In A High Risk Population Presenting To A Major Tertiary Care Center In Pakistan, Namrah Anwar, Shahid Pervez, Qurratulain Chundriger, Mohammad Sohail Awan, Tariq Moatter, Tazeen Saeed Ali

Department of Pathology and Laboratory Medicine

Oral squamous cell carcinoma (OSCC) has the highest prevalence in head and neck cancers and is the first and second most common cancer in males and females of Pakistan respectively. Major risk factors include peculiar chewing habits like areca nut, betel quid, and tobacco. The majority of OSCC presents at an advanced stage with poor prognosis. On the face of such a high burden of this preventable cancer, there is a relative lack of recent robust data and its association with known risk factors from Pakistan. The aim of this study was to identify the socioeconomic factors and clinicopathological features …


Risk Of New Bloodstream Infections And Mortality Among People Who Inject Drugs With Infective Endocarditis., Charlie Tan, Esfandiar Shojaei, Joshua C. Wiener, Meera Shah, Sharon Koivu, Michael Silverman Aug 2020

Risk Of New Bloodstream Infections And Mortality Among People Who Inject Drugs With Infective Endocarditis., Charlie Tan, Esfandiar Shojaei, Joshua C. Wiener, Meera Shah, Sharon Koivu, Michael Silverman

Epidemiology and Biostatistics Publications

IMPORTANCE: People who inject drugs (PWID) who are being treated for infective endocarditis remain at risk of new bloodstream infections (BSIs) due to ongoing intravenous drug use (IVDU).

OBJECTIVES: To characterize new BSIs in PWID receiving treatment for infective endocarditis, to determine the clinical factors associated with their development, and to determine whether new BSIs and treatment setting are associated with mortality.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was performed at 3 tertiary care hospitals in London, Ontario, Canada, from April 1, 2007, to March 31, 2018. Participants included a consecutive sample of all PWID 18 years or …


Early Working Memory Is A Significant Predictor Of Verbal And Processing Skills At 6-7 Years In Children Born Extremely Preterm, Jean Lowe, Carla M Bann, Janell Fuller, Betty R Vohr, Susan R Hintz, Abhik Das, Rosemary D Higgins, Kristi L Watterberg, Support Study Group Of The Eunice Kennedy Shriver National Institute Of Child Health And Human Development Neonatal Research Network Aug 2020

Early Working Memory Is A Significant Predictor Of Verbal And Processing Skills At 6-7 Years In Children Born Extremely Preterm, Jean Lowe, Carla M Bann, Janell Fuller, Betty R Vohr, Susan R Hintz, Abhik Das, Rosemary D Higgins, Kristi L Watterberg, Support Study Group Of The Eunice Kennedy Shriver National Institute Of Child Health And Human Development Neonatal Research Network

Pediatrics Research and Scholarship

OBJECTIVE: The study was designed to investigate whether attainment of object permanence, a measure of early working memory used at 18-22 months corrected age, was associated with executive function at 6-7 years in a cohort of children born extremely preterm.

STUDY DESIGN: Children enrolled in the Neuroimaging and Neurodevelopmental Outcome (NEURO) study, a secondary study to the Surfactant Positive Airway Pressure and Pulse Oximetry Trial (SUPPORT) of the NICHD NRN, were eligible for this longitudinal study. Testing completed at 18 to 22 months corrected age was compared to testing at school age with a specific focus on measures of executive …


White Matter Abnormalities Across Different Epilepsy Syndromes In Adults: An Enigma-Epilepsy Study, Sean N. Hatton, Khoa H. Huynh, Leonardo Bonilha, Eugenio Abela, Saud Alhusaini, Andre Altmann, Marina K. M. Alvim, Akshara R. Balachandra, Emanuele Bartolini, Benjamin Bender, Neda Bernasconi, Andrea Bernasconi, Boris Bernhardt, Núria Bargallo, Benoit Caldairou, Maria E. Caligiuri, Sarah J. A. Carr, Gianpiero L. Cavalleri, Fernando Cendes, Luis Concha, Esmaeil Davoodi-Bojd, Patricia M. Desmond, Orrin Devinsky, Colin P. Doherty, Martin Domin, John S. Duncan, Niels K. Focke, Sonya F. Foley, Antonio Gambardella, Ezequiel Gleichgerrcht, Renzo Guerrini, Khalid Hamandi, Akari Ishikawa, Simon S. Keller, Peter V. Kochunov, Raviteja Kotikalapudi, Barbara A.K. Kreilkamp, Patrick Kwan, Angelo Labate, Soenke Langner, Matteo Lenge, Min Liu, Elaine Lui, Pascal Martin, Mario Mascalchi, José C.V. Moreira, Marcia E. Morita-Sherman, Terence J. O'Brien, Heath R. Pardoe, José C. Pariente, Letícia F. Ribeiro, Mark P. Richardson, Cristiane S. Rocha, Raúl Rodríguez-Cruces, Felix Rosenow, Mariasavina Severino, Benjamin Sinclair, Hamid Soltanian-Zadeh, Pasquale Striano, Peter N. Taylor, Rhys H. Thomas, Domenico Tortora, Dennis Velakoulis, Annamaria Vezzani, Lucy Vivash, Felix Von Podewils, Sjoerd B. Vos, Bernd Weber, Gavin P. Winston, Clarissa L. Yasuda, Alyssa H. Zhu, Paul M. Thompson, Christopher D. Whelan, Neda Jahanshad, Sanjay M. Sisodiya, Carrie R. Mcdonald Aug 2020

White Matter Abnormalities Across Different Epilepsy Syndromes In Adults: An Enigma-Epilepsy Study, Sean N. Hatton, Khoa H. Huynh, Leonardo Bonilha, Eugenio Abela, Saud Alhusaini, Andre Altmann, Marina K. M. Alvim, Akshara R. Balachandra, Emanuele Bartolini, Benjamin Bender, Neda Bernasconi, Andrea Bernasconi, Boris Bernhardt, Núria Bargallo, Benoit Caldairou, Maria E. Caligiuri, Sarah J. A. Carr, Gianpiero L. Cavalleri, Fernando Cendes, Luis Concha, Esmaeil Davoodi-Bojd, Patricia M. Desmond, Orrin Devinsky, Colin P. Doherty, Martin Domin, John S. Duncan, Niels K. Focke, Sonya F. Foley, Antonio Gambardella, Ezequiel Gleichgerrcht, Renzo Guerrini, Khalid Hamandi, Akari Ishikawa, Simon S. Keller, Peter V. Kochunov, Raviteja Kotikalapudi, Barbara A.K. Kreilkamp, Patrick Kwan, Angelo Labate, Soenke Langner, Matteo Lenge, Min Liu, Elaine Lui, Pascal Martin, Mario Mascalchi, José C.V. Moreira, Marcia E. Morita-Sherman, Terence J. O'Brien, Heath R. Pardoe, José C. Pariente, Letícia F. Ribeiro, Mark P. Richardson, Cristiane S. Rocha, Raúl Rodríguez-Cruces, Felix Rosenow, Mariasavina Severino, Benjamin Sinclair, Hamid Soltanian-Zadeh, Pasquale Striano, Peter N. Taylor, Rhys H. Thomas, Domenico Tortora, Dennis Velakoulis, Annamaria Vezzani, Lucy Vivash, Felix Von Podewils, Sjoerd B. Vos, Bernd Weber, Gavin P. Winston, Clarissa L. Yasuda, Alyssa H. Zhu, Paul M. Thompson, Christopher D. Whelan, Neda Jahanshad, Sanjay M. Sisodiya, Carrie R. Mcdonald

Research Administration Articles

The epilepsies are commonly accompanied by widespread abnormalities in cerebral white matter. ENIGMA-Epilepsy is a large quantitative brain imaging consortium, aggregating data to investigate patterns of neuroimaging abnormalities in common epilepsy syndromes, including temporal lobe epilepsy, extratemporal epilepsy, and genetic generalized epilepsy. Our goal was to rank the most robust white matter microstructural differences across and within syndromes in a multicentre sample of adult epilepsy patients. Diffusion-weighted MRI data were analysed from 1069 healthy controls and 1249 patients: temporal lobe epilepsy with hippocampal sclerosis (n = 599), temporal lobe epilepsy with normal MRI (n = 275), genetic generalized epilepsy (n …


Nanoceria Distribution And Effects Are Mouse-Strain Dependent, Robert A. Yokel, Michael T. Tseng, D. Allan Butterfield, Matthew L. Hancock, Eric A. Grulke, Jason M. Unrine, Arnold J. Stromberg, Alan K. Dozier, Uschi M. Graham Aug 2020

Nanoceria Distribution And Effects Are Mouse-Strain Dependent, Robert A. Yokel, Michael T. Tseng, D. Allan Butterfield, Matthew L. Hancock, Eric A. Grulke, Jason M. Unrine, Arnold J. Stromberg, Alan K. Dozier, Uschi M. Graham

Pharmaceutical Sciences Faculty Publications

Prior studies showed nanoparticle clearance was different in C57BL/6 versus BALB/c mice, strains prone to Th1 and Th2 immune responses, respectively. Objective: Assess nanoceria (cerium oxide, CeO2 nanoparticle) uptake time course and organ distribution, cellular and oxidative stress, and bioprocessing as a function of mouse strain. Methods: C57BL/6 and BALB/c female mice were i.p. injected with 10 mg/kg nanoceria or vehicle and terminated 0.5 to 24 h later. Organs were collected for cerium analysis; light and electron microscopy with elemental mapping; and protein carbonyl, IL-1β, and caspase-1 determination. Results: Peripheral organ cerium significantly increased, generally more …


Post-Registration Experience Of Nivolumab In Advanced Hepatocellular Carcinoma: An International Study, Petros Fessas, Ahmed Kaseb, Yinghong Wang, Anwaar Saeed, David Szafron, Tomi Jun, Sirish Dharmapuri, Abdul Rafeh Naqash, Mahvish Muzaffar, Musharraf Navaid, Uqba Khan, Chiehju Lee, Anushi Bulumulle, Bo Yu, Sonal Paul, Neil Nimkar, Dominik Bettinger, Francesca Benevento, Hannah Hildebrand, Tiziana Pressiani, Yehia I Abugabal, Nicola Personeni, Yi-Hsiang Huang, Lorenza Rimassa, Celina Ang, Thomas Marron, David J Pinato Aug 2020

Post-Registration Experience Of Nivolumab In Advanced Hepatocellular Carcinoma: An International Study, Petros Fessas, Ahmed Kaseb, Yinghong Wang, Anwaar Saeed, David Szafron, Tomi Jun, Sirish Dharmapuri, Abdul Rafeh Naqash, Mahvish Muzaffar, Musharraf Navaid, Uqba Khan, Chiehju Lee, Anushi Bulumulle, Bo Yu, Sonal Paul, Neil Nimkar, Dominik Bettinger, Francesca Benevento, Hannah Hildebrand, Tiziana Pressiani, Yehia I Abugabal, Nicola Personeni, Yi-Hsiang Huang, Lorenza Rimassa, Celina Ang, Thomas Marron, David J Pinato

Faculty, Staff and Students Publications

BACKGROUND: Nivolumab is Food and Drug Administration approved in sorafenib-experienced, advanced hepatocellular carcinoma (HCC). Post-registration data of treatment in a real-world setting is lacking.

PATIENTS AND METHODS: We performed an international, multicenter observational study to confirm safety and efficacy of nivolumab in 233 patients treated outside clinical trials from eight centers in North America, Europe and Asia.

RESULTS: Patients received nivolumab for Barcelona Clinic Liver Cancer stage C (n=191, 92.0%) and Child-Pugh (CP) A (n=158, 67.8%) or B (n=75, 32.2%) HCC as first (n=85, 36.5%) or second to fourth systemic therapy line …


Prevalence Of Helicobacter Pylori Positive Non-Cardia Gastric Adenocarcinoma Is Low And Decreasing In A Us Population, Theresa H Nguyen, Niharika Mallepally, Tariq Hammad, Yan Liu, Aaron P Thrift, Hashem B El-Serag, Mimi C Tan Aug 2020

Prevalence Of Helicobacter Pylori Positive Non-Cardia Gastric Adenocarcinoma Is Low And Decreasing In A Us Population, Theresa H Nguyen, Niharika Mallepally, Tariq Hammad, Yan Liu, Aaron P Thrift, Hashem B El-Serag, Mimi C Tan

Faculty, Staff and Students Publications

BACKGROUND: Helicobacter pylori infection is an established causal factor for non-cardia gastric cancer. H. pylori negative gastric cancer prevalence among US patients is unclear.

METHODS: This retrospective cohort study examined H. pylori prevalence among consecutive patients with incident non-cardia gastric adenocarcinoma at the Houston VA Hospital (11/2007-10/2018). H. pylori positivity was defined by H. pylori on histopathology, positive antibody serology, stool antigen, or urea breath testing. We examined for trends in H. pylori negative gastric cancer based on year of diagnosis. Associations between histopathologic and cancer-related outcomes with H. pylori positivity were determined using regression models.

RESULTS: Of 91 patients …


Modulation Of Hedgehog Signaling By Kappa Opioids To Attenuate Osteoarthritis, Alexander E Weber, Omid Jalali, Sean Limfat, Ruzanna Shkhyan, Robert Van Der Horst, Siyoung Lee, Yucheng Lin, Liangliang Li, Erik N Mayer, Liming Wang, Nancy Q Liu, Frank A Petrigliano, Jay R Lieberman, Denis Evseenko Aug 2020

Modulation Of Hedgehog Signaling By Kappa Opioids To Attenuate Osteoarthritis, Alexander E Weber, Omid Jalali, Sean Limfat, Ruzanna Shkhyan, Robert Van Der Horst, Siyoung Lee, Yucheng Lin, Liangliang Li, Erik N Mayer, Liming Wang, Nancy Q Liu, Frank A Petrigliano, Jay R Lieberman, Denis Evseenko

Faculty, Staff and Students Publications

OBJECTIVE: Inhibition of hedgehog (HH) signaling prevents cartilage degeneration and promotes repair in animal models of osteoarthritis (OA). This study, undertaken in OA models and in human OA articular cartilage, was designed to explore whether kappa opioid receptor (KOR) modulation via the inhibition of HH signaling may have therapeutic potential for achieving disease-modifying activity in OA.

METHODS: Primary human articular cartilage and synovial tissue samples from patients with knee OA undergoing total joint replacement and from healthy human subjects were obtained from the National Disease Research Interchange. For in vivo animal studies, a partial medial meniscectomy (PMM) model of knee …


Combinatorial Pharmacogenomic Algorithm Is Predictive Of Citalopram And Escitalopram Metabolism In Patients With Major Depressive Disorder, Richard C. Shelton, Charles R. Conway, Et Al. Aug 2020

Combinatorial Pharmacogenomic Algorithm Is Predictive Of Citalopram And Escitalopram Metabolism In Patients With Major Depressive Disorder, Richard C. Shelton, Charles R. Conway, Et Al.

2020-Current year OA Pubs

Pharmacogenomic tests used to guide clinical treatment for major depressive disorder (MDD) must be thoroughly validated. One important assessment of validity is the ability to predict medication blood levels, which reflect altered metabolism. Historically, the metabolic impact of individual genes has been evaluated; however, we now know that multiple genes are often involved in medication metabolism. Here, we evaluated the ability of individual pharmacokinetic genes (CYP2C19, CYP2D6, CYP3A4) and a combinatorial pharmacogenomic test (GeneSight Psychotropic®; weighted assessment of all three genes) to predict citalopram/escitalopram blood levels in patients with MDD. Patients from the Genomics Used to Improve DEpression Decisions (GUIDED) …