Digital Commons Network^™

Inter-Subject Correlation While Listening To Minimalist Music: A Study Of Electrophysiological And Behavioral Responses To Steve Reich’S Piano Phase, Tysen Dauer, Duc T. Nguyen, Nick Gang, Jacek P. Dmochowski, Jonathan Berger, Blair Kaneshiro

Publications and Research

Musical minimalism utilizes the temporal manipulation of restricted collections of rhythmic, melodic, and/or harmonic materials. One example, Steve Reich’s Piano Phase, offers listeners readily audible formal structure with unpredictable events at the local level. For example, pattern recurrences may generate strong expectations which are violated by small temporal and pitch deviations. A hyper-detailed listening strategy prompted by these minute deviations stands in contrast to the type of listening engagement typically cultivated around functional tonal Western music. Recent research has suggested that the inter-subject correlation (ISC) of electroencephalographic (EEG) responses to natural audio-visual stimuli objectively indexes a state of “engagement,” demonstrating …

Violation Of Magnetic Flux Conservation By Superconducting Nanorings, Iris Mowgood, Gurgen Melkonyan, Rajendra Dulal, Serafim Teknowijoyo, Sara Chahid, Armen Gulian

Mathematics, Physics, and Computer Science Faculty Articles and Research

The behavior of magnetic flux in the ring-shaped finite-gap superconductors is explored from the view-point of the flux-conservation theorem which states that under the variation of external magnetic field "the magnetic flux through the ring remains constant" (see, e.g., [L.D. Landau and E.M. Lifshitz, Electrodynamics of Continuos Media, vol. 8 (New York, Pergamon Press, 1960), Section 42]). Our results, based on the time-dependent Ginzburg-Landau equations and COMSOL modeling, made it clear that in the general case, this theorem is incorrect. While for rings of macroscopic sizes the corrections are small, for micro and nanorings they become rather substantial. The physical …

Stroke Depression And Rehabilitation Willingness: Benchmark Study, India J. Lewis

MSN Capstone Projects

The purpose of this paper is to examine, identify, and treat patients with post-stroke depression. Post-stroke depression can affect a patient's willingness to perform activities of daily living, this may result in poor functional outcomes on discharge. Depression is not regularly screened during the acute stroke phase, therefore not regularly treated with the intent to improve functional outcomes. The Patient Health screening questionnaire (PHQ-9) is an available tool that can assist in recognizing and treating depression. This project will determine that the current literature supports implementation of a protocol needed to improve rehabilitation participation.

Non-Linear Optical Characterization Of Stressed Materials, Kaylee N. Rellaford

Theses and Dissertations

Interactions between materials, their surfaces, and applied stresses are involved in every man-made construction in the world. Therefore, finding ways to interact without altering inherent properties of materials is of great interest. Surface spectroscopies, including second harmonic generation (SHG) and sum frequency generation (SFG), are inherently noninvasive testing methods. Both SHG and SFG are well-developed techniques that can be used in various applications including the characterization of material state. Both of these techniques allow for a noninvasive analysis of various materials, such as metals and polymers. We have used SHG as a method to characterize the change in signal strength …

Evidence Of Myomir Regulation Of The Pentose Phosphate Pathway During Mechanical Load-Induced Hypertrophy, Taylor Valentino, Vandre C. Figueiredo, C. Brooks Mobley, John J. Mccarthy, Ivan J. Vechetti Jr.

Physiology Faculty Publications

Many of the molecular and cellular mechanisms discovered to regulate skeletal muscle hypertrophy were first identified using the rodent synergist ablation model. This model reveals the intrinsic capability and necessary pathways of skeletal muscle growth in response to mechanical overload (MOV). Reminiscent of the rapid cellular growth observed with cancer, we hypothesized that in response to MOV, skeletal muscle would undergo metabolic programming to sustain increased demands to support hypertrophy. To test this hypothesis, we analyzed the gene expression of specific metabolic pathways taken from transcriptomic microarray data of a MOV time course. We found an upregulation of genes involved …

Enhancing Situational Awareness For Rotorcraft Pilots Using Virtual And Augmented Reality, Ardit Pranvoku

Theses and Dissertations

Rotorcraft pilots often face the challenge of processing a multitude of data, integrating it with prior experience and making informed decisions in complex, rapidly changing multisensory environments. Virtual Reality (VR), and more recently Augmented Reality (AR) technologies have been applied for providing users with immersive, interactive and navigable experiences. The research work described in this thesis demonstrates that VR/AR are particularly effective in providing real-time information without detracting from the pilot's mission in both civilian and military engagements. The immersion of the pilot inside of the VR model provides enhanced realism. Interaction with the VR environment allows pilots to practice …

Implementation Of A Pre-Anesthesia Take-Home Evaluation (Pathe) As A Means Of Process Improvement: A Best Practice Recommendation, Russell Gray, Hunter Brown, Trey Galloway

Doctoral Projects

The pre-anesthesia evaluation (PAE) is a vital component to anesthesia providers when choosing an appropriate anesthetic plan for patients requiring surgery. The PAE, pre-anesthesia risk-factor assessment, and provision of pre-anesthesia instructions are standards of care implemented in order to assess the patient’s likely outcome of surgery and anesthesia as well as stratify any known risk factors to optimize surgical/anesthetic outcomes. Any disruption in this process could potentially lead to decreased patient/provider satisfaction, reduced patient compliance with pre-anesthetic instructions, reduced patient safety, and unnecessary financial burden.

After the completion of a literature review, the need for a best practice recommendation was …

Implementation And Evaluation Of A Registered Nurse Pre-Eclampsia Education Program Within A Women's Urgent Care Center, Amber Vetter

Doctoral Projects

Pre-eclampsia can be a serious development for both mother and fetus during pregnancy. Increased mortality and morbidity rates have been shown in women diagnosed with pre-eclampsia. Higher education for registered nurses on a Women’s Urgent Care (WUC) center will help diagnose the mother more quickly and inevitably receive treatment sooner leading to better outcomes for the birth of her newborn. The educational tools used in the study were a pre-and post-test and an educational video for the registered nurses to watch. A retrospective chart review before and after the intervention will help to see if there is any decrease in …

Evidence-Based Update In Practice Development Of A Nursing Checklist For Documentation Of Pediatric Pre-Operative Fall Safety Measures, Susan Shemper

Doctoral Projects

ABSTRACT

Fall safety is an important component of patient care in the healthcare setting. Communication and implementation of fall safety measures are a critical part of the plan of care for each patient. Pre-operative pediatric patients have an increased risk of falls due to sedation, under-developed motor skills, and fall safety education. It is important for the pre-operative nursing staff to evaluate and implement a plan of care, including fall safety measures, according to each patient’s needs. The Joint Commission, (additionally known as TJC), is a United States based nonprofit, tax-exempt 501(c)(3) organization that accredits more than 22,000 U.S. healthcare …

A Survey Of Delirium Self-Reported Knowledge And Practices Among Emergency Physicians In The United States, Anita N. Chary, Adriane Lesser, Sharon K. Inouye, Christopher R. Carpenter Md, Msc, Amy R. Stuck, Maura Kennedy

Journal of Geriatric Emergency Medicine

Objective: This study aimed to evaluate United States emergency physicians’ self-reported knowledge and practices regarding the detection, prevention, and management of delirium, a common and deadly syndrome that disproportionately affects older emergency department (ED) patients. Knowledge and practices of the broader emergency physician community about these priority topics in geriatric emergency medicine are understudied.

Design: Electronic self-administered online survey

Setting: United States

Participants: One-hundred ninety-seven emergency physicians of the American College of Emergency Physicians Emergency Medicine Practice Research Network

Measures: Descriptive statistics were generated from survey responses.

Results: Of 734 physicians in the research network who were sent the …

An Occupation-Based Program For Formerly Incarcerated Youth And Staff In An Employment Re-Integration Program, Heather Fierros, Angela Blackwell, Leslie Khan-Farooqi

Fall 2021 Virtual OTD Capstone Symposium

One of the most vulnerable and growing populations within the United States (U.S.) are youth involved in the juvenile justice system. Each day, approximately 60,000 youth are currently incarcerated in the U.S., signifying a necessary demand for community re-entry success. Having been incarcerated makes it more challenging for youth to attend school, obtain a license, find public housing, and attain public benefits. Furthermore, because of the effects following being a part of the juvenile justice system, the youth exemplify a lack of social interaction skills, hindered relationship patterns, altered values and beliefs. These underdeveloped skills and patterns interfere with the …

Staff Perceptions On Organizational Change And Its Impact On Occupational Participation In Institutional Settings, Shelby Pearce, Susan Macdermott, Karen Park

Fall 2021 Virtual OTD Capstone Symposium

Background: Organizational change, primarily in institutional settings, is necessary to prevent institutionalization as well as to reach the goals of the organizations. To support these goals, institutional settings, such as correctional facilities, often use restrictive measures including occupational deprivation. As a profession, occupational therapy recognizes the importance of occupational participation for all persons in society, however there is a gap in knowledge on the importance of how to promote and/or educate other entities on successful change management in different institutional settings.

Purpose: The purpose of this study is to understand how organizational culture impacts occupational participation in institutional settings and …

C. S. Lewis And His Later Respondents: Letting In Fresh Air, Preventing Questions, And Reimagining A Preface To Paradise Lost, David V. Urban

University Faculty Publications and Creative Works

This essay chronicles significant responses to C. S. Lewis’s A Preface to Paradise Lost (1942) that occurred from the 1960s into the twenty-first century. Important responses include those of William Empson, Stanley Fish, Stuart Curran, John Rumrich, Peter C. Herman, Michael Bryson, and Joseph Wittreich. All of these scholars challenged Lewis on various points—most commonly concerning matters of Lewis’s analysis of Milton’s Satan, his alleged oversimplification of Milton’s theologically complex epic, the supposed similarities between A Preface and Fish’s Surprised by Sin, and his assumed hegemonic prevention of new avenues of critical inquiry into Milton’s epic. This essay contends …

Defects Analysis And Root Cause Robustness Of Product Labels Of An Acaricide Product In East Africa, Moses Okal Ogodo, Z Ekeocha, S Byrn, K Clase

BIRS Africa Technical Report Papers

This project aimed at investigating online damages of packaging materials generated during production because of imperfectness of production processes. These online damages may lead to upsurge in production cost and/or market returns, causing the company to experience losses and even damage its reputation. Data on online damages were collected for 20ml, 40ml and 100ml labels of an acaricide product for the period between July 2018 and June 2019 and statistically analyzed. Investigation was done on the causes of online damages, then corrective and preventive actions carried out. Analysis of online damages of labels of the three pack sizes revealed a …

Medicines Regulation In West Africa: Current State And Opportu-Nities, Oluwafunmike Sopein-Mann, Z Ekeocha, S Byrn, K Clase

BIRS Africa Technical Report Papers

Ndomondo-Sigonda et al. (2017) observed that there is scarcity of information on human resources (person-nel devoted to regulation of medicines) in the domain of medicines regulation in the sub-Saharan Africa (SSA). The published information on medicines regulation by the National Medicines Regulatory Authorities (NMRAs) in the Economic Community of West African States (ECOWAS) region are no longer current and consistent with the current realities in the NMRAs. In order to reveal this occurrence, show the trends that exist over the years and make appropriate recommendations, data were collected and compared from 2005, 2010 and 2017 research reports on seven regulatory …

Quality Of Sample Testing In The Laboratory Unit: Current Situation And Strategies For Improvement, Aloyce Constantine, Z Ekeocha, S Byrn, K Clase

BIRS Africa Technical Report Papers

The purpose of this study was to understand the status quo of quality sample testing in the laboratory unit. A quantitative research method was used. An extensive laboratory documents (protocol, worksheets, laboratory analytical plan, standard operating procedures and manuals) review was performed and a networking approach to both management and lab staff at all levels was reviewed in order to identify all non-conformities occurred in the past three years. Results identified 36 number of results deviated from reference standards among different test performed, 400 number of samples lost, the number of laboratory personnel who were not sufficiently trained to take …

Pharmaceutical Industry In Uganda: A Review Of The Common Gmp Non-Conformances During Regulatory Inspections, Nasser Lubowa, Z Ekeocha, S Byrn, K Clase

BIRS Africa Technical Report Papers

The prevalence of substandard medicines in Africa is high but not well documented. Low and Middle-Income Countries (LMICs) are likely to face considerable challenges with substandard medications. Africa faces inadequate drug regulatory practices, and in general, compliance with Good Manufacturing Practices (GMP) in most of the pharmaceutical industries is lacking. The majority of pharmaceutical manufacturers in developing countries are often overwhelmed by the GMP requirements and therefore are unable to operate in line with internationally acceptable standards. Non-conformances observed during regulatory inspections provide the status of the compliance to GMP requirements. The study aimed to identify the GMP non-conformances during …

The Impact Of Mentoring As A Gmp Capability Building Tool In The Pharmaceutical Manufacturing Industry In Nigeria, Monica Agu, Z Ekeocha, S Byrn, K Clase

BIRS Africa Technical Report Papers

Good Manufacturing Practices (GMP), a component of Pharmaceutical Quality Systems, is aimed primarily at managing and minimizing the risks inherent in pharmaceutical manufacture to ensure the quality, safety and efficacy of products. Provision of adequate number of personnel with the necessary qualifications/practical experience and their continuous training and evaluation of effectiveness of the training is the responsibility of the manufacturer. (World Health Organization [WHO], 2014; International Organization for Standardization [ISO], 2015). The classroom method of training that has been used for GMP capacity building in the pharmaceutical manufacturing industry in Nigeria over the years, delivered by experts from stringently regulated …

Retrospective Study Of Inspectors Competency In The Act Of Writing Gmp Inspection Report, Chidi Uche, Z Ekeocha, S Byrn, K Clase

BIRS Africa Technical Report Papers

The research was a retrospective study of twenty-five Good Manufacturing Practice (GMP) inspection reports (from March 2017 through to December 2018) of a national medicine regulatory agency, drug Inspectorate, in West Africa, designed to assess the inspectors’ expertise in the act of inspection report writing. The investigation examined a paper-based tool of thirteen pre-registration Inspection reports and twelve GMP reassessment reports written prior and following an intervention program by external GMP trainers to enhance inspectors’ skill in pharmaceutical cGMP inspection. The study made use of quantitative analysis to investigate each team’s expertise in the act of writing GMP inspection report. …

Strategies For Teaching Based On Autism Research (Star Program) Curriculum Review And Implementation, Cassidy Harrington

Dissertations, Theses, and Projects

Autism Spectrum Disorder (ASD) is becoming more prevalent in school systems. Researchers began tracking the prevalence of ASD in the year 2000. It is estimated that 1 in 68 children have ASD in the United States of America (1 in 42 prevalence for boys and 1 in 189 prevalence for girls) (Landa, 2018). Medically a child can be diagnosed with ASD but school systems themselves are not able to formally diagnose ASD in children. (ECTA, 2012). ASD can be hard to diagnose as some cases are more severe than others and the earlier that a child is found to have …

The Impact Of Small Group Direct Instruction On The Vocabulary Development Of Fourth Grade Students, Rachel Solum

Dissertations, Theses, and Projects

This 2021 study focused on the impact that small group vocabulary instruction had on the vocabulary development of 4th grade students. I wanted to see the effect that small group instruction had on students’ vocabulary growth. Students were pulled into a small group every day for four straight weeks. There was four groups of four students involved. During this small group time the teacher pulled vocabulary words from the word wall. The words on the word wall were tier two vocabulary words that had been pulled from various interactive read alouds. The teacher followed Marzano’s Six Step Approach to teaching …

Self-Efficacy: Nurses’ Perceptions Of Caring For Patients Living With Diabetes, Victoria Y. Mccue

Nursing & Health Sciences Research Journal

Introduction: Diabetes is an epidemic that affects over 415 million people worldwide. In the United States, the number of people diagnosed with diabetes is projected to triple to over 60 million by 2060. With this surge, the number of hospitalizations across the country has significantly increased. Direct care nurses play a vital role in the management of patients living with diabetes. The purpose of this research study was to explore and describe medical-surgical nurses’ perceptions of self-efficacy related to caring for patients living with diabetes. This study's guiding research question was: What are nurses’ perceptions on the influences that impact …

The Cowl - V. 86 N. 10 - Dec 9, 2021

The Cowl

The Cowl - student newspaper of Providence College. Vol. 86 No. 10 - December 9, 2021. 40 pages.

Error Propagation And Algorithmic Design Of Contour Integral Eigensolvers With Applications To Fiber Optics, Benjamin Quanah Parker

Dissertations and Theses

In this work, the finite element method and the FEAST eigensolver are used to explore applications in fiber optics. The present interest is in computing eigenfunctions u and propagation constants β satisfing [sic] the Helmholtz equation Δu + k²n²u = β²u. Here, k is the freespace wavenumber and n is a spatially varying coefficient function representing the refractive index of the underlying medium. Such a problem arises when attempting to compute confinement losses in optical fibers that guide laser light. In practice, this requires the computation of functions u referred to as …

At-Sensor Radiometric Correction Of A Multispectral Camera (Rededge) For Suas Vegetation Mapping, Cuizhen Wang

Faculty Publications

Rapid advancement of drone technology enables small unmanned aircraft systems (sUAS) for quantitative applications in public and private sectors. The drone-mounted 5-band MicaSense RedEdge cameras, for example, have been popularly adopted in the agroindustry for assessment of crop healthiness. The camera extracts surface reflectance by referring to a pre-calibrated reflectance panel (CRP). This study tests the performance of a Matrace100/RedEdge-M camera in extracting surface reflectance orthoimages. Exploring multiple flights and field experiments, an at-sensor radiometric correction model was developed that integrated the default CRP and a Downwelling Light Sensor (DLS). Results at three vegetated sites reveal that the current CRP-only …

Late Cretaceous Paleoceanographic Evolution And The Onset Of Cooling In The Santonian At Southern High Latitudes (Iodp Site U1513, Se Indian Ocean), Maria Rose Petrizzo, Kenneth G. Macleod, David K. Watkins, Erik Wolfgring, Brian T. Huber

Department of Earth and Atmospheric Sciences: Faculty Publications

The latest Cenomanian to Santonian sedimentary record recovered at IODP Expedition 369 Site U1513 in the Mentelle Basin (SE Indian Ocean, paleolatitude 60°S at 85 Ma) is studied to interpret the paleoceanographic evolution in the Southern Hemisphere. The planktonic foraminiferal assemblage changes, the depth ecology preferences of different species, and the surface and seafloor temperature inferred from the stable isotopic values measured on foraminiferal tests provide meaningful information to the understanding of the Late Cretaceous climate. The hothouse climate during the Turonian-Santonian, characterized by weak latitudinal temperature gradients and high atmospheric CO₂ concentrations, is followed by a progressive cooling …

Nutrient Intake And Dietary Inflammatory Potential In Current And Recovered Anorexia Nervosa, Olivia Patsalos, Bethan Dalton, Christia Kyprianou, Joseph Firth, Nitin Shivappa Mbbs, Mph, Ph.D., James Hébert Scd, Ulrike Schmidt, Hubertus Himmerich

Faculty Publications

Anorexia nervosa (AN) is characterised by disrupted and restrictive eating patterns. Recent investigations and meta-analyses have found altered concentrations of inflammatory markers in people with current AN. We aimed to assess nutrient intake in participants with current or recovered AN, as compared to healthy individuals, and explore group differences in dietary inflammatory potential as a possible explanation for the observed alterations in inflammatory markers. We recruited participants with current AN (n = 51), those recovered from AN (n = 23), and healthy controls (n = 49). We used the Food Frequency Questionnaire (FFQ), to calculate a Dietary …

Meta-Analyses Identify Dna Methylation Associated With Kidney Function And Damage, Pascal Schlosser, Adrienne Tin, Pamela R Matias-Garcia, Chris H L Thio, Roby Joehanes, Hongbo Liu, Antoine Weihs, Zhi Yu, Anselm Hoppmann, Franziska Grundner-Culemann, Josine L Min, Adebowale A Adeyemo, Charles Agyemang, Johan Ärnlöv, Nasir A Aziz, Andrea Baccarelli, Murielle Bochud, Hermann Brenner, Monique M B Breteler, Cristian Carmeli, Layal Chaker, John C Chambers, Shelley A Cole, Josef Coresh, Tanguy Corre, Adolfo Correa, Simon R Cox, Niek De Klein, Graciela E Delgado, Arce Domingo-Relloso, Kai-Uwe Eckardt, Arif B Ekici, Karlhans Endlich, Kathryn L Evans, James S Floyd, Myriam Fornage, Lude Franke, Eliza Fraszczyk, Xu Gao, Xīn Gào, Mohsen Ghanbari, Sahar Ghasemi, Christian Gieger, Philip Greenland, Megan L Grove, Sarah E Harris, Gibran Hemani, Peter Henneman, Christian Herder, Steve Horvath, Lifang Hou, Mikko A Hurme, Shih-Jen Hwang, Marjo-Riitta Jarvelin, Sharon L R Kardia, Silva Kasela, Marcus E Kleber, Wolfgang Koenig, Jaspal S Kooner, Holly Kramer, Florian Kronenberg, Brigitte Kühnel, Terho Lehtimäki, Lars Lind, Dan Liu, Yongmei Liu, Donald M Lloyd-Jones, Kurt Lohman, Stefan Lorkowski, Ake T Lu, Riccardo E Marioni, Winfried März, Daniel L Mccartney, Karlijn A C Meeks, Lili Milani, Pashupati P Mishra, Matthias Nauck, Ana Navas-Acien, Christoph Nowak, Annette Peters, Holger Prokisch, Bruce M Psaty, Olli T Raitakari, Scott M Ratliff, Alex P Reiner, Sylvia E Rosas, Ben Schöttker, Joel Schwartz, Sanaz Sedaghat, Jennifer A Smith, Nona Sotoodehnia, Hannah R Stocker, Silvia Stringhini, Johan Sundström, Brenton R Swenson, Maria Tellez-Plaza, Joyce B J Van Meurs, Jana V Van Vliet-Ostaptchouk, Andrea Venema, Niek Verweij, Rosie M Walker, Matthias Wielscher, Juliane Winkelmann, Bruce H R Wolffenbuttel, Wei Zhao, Yinan Zheng, Marie Loh, Harold Snieder, Daniel Levy, Melanie Waldenberger, Katalin Susztak, Anna Köttgen, Alexander Teumer

Faculty, Staff and Student Publications

Chronic kidney disease is a major public health burden. Elevated urinary albumin-to-creatinine ratio is a measure of kidney damage, and used to diagnose and stage chronic kidney disease. to extend the knowledge on regulatory mechanisms related to kidney function and disease, we conducted a blood-based epigenome-wide association study for estimated glomerular filtration rate (n = 33,605) and urinary albumin-to-creatinine ratio (n = 15,068) and detected 69 and seven CpG sites where DNA methylation was associated with the respective trait. The majority of these findings showed directionally consistent associations with the respective clinical outcomes chronic kidney disease and moderately increased albuminuria. …

Epigenome-Wide Association Study Of Serum Urate Reveals Insights Into Urate Co-Regulation And The Slc2a9 Locus, Adrienne Tin, Pascal Schlosser, Pamela R Matias-Garcia, Chris H L Thio, Roby Joehanes, Hongbo Liu, Zhi Yu, Antoine Weihs, Anselm Hoppmann, Franziska Grundner-Culemann, Josine L Min, Victoria L Halperin Kuhns, Adebowale A Adeyemo, Charles Agyemang, Johan Ärnlöv, Nasir A Aziz, Andrea Baccarelli, Murielle Bochud, Hermann Brenner, Jan Bressler, Monique M B Breteler, Cristian Carmeli, Layal Chaker, Josef Coresh, Tanguy Corre, Adolfo Correa, Simon R Cox, Graciela E Delgado, Kai-Uwe Eckardt, Arif B Ekici, Karlhans Endlich, James S Floyd, Eliza Fraszczyk, Xu Gao, Xīn Gào, Allan C Gelber, Mohsen Ghanbari, Sahar Ghasemi, Christian Gieger, Philip Greenland, Megan L Grove, Sarah E Harris, Gibran Hemani, Peter Henneman, Christian Herder, Steve Horvath, Lifang Hou, Mikko A Hurme, Shih-Jen Hwang, Sharon L R Kardia, Silva Kasela, Marcus E Kleber, Wolfgang Koenig, Jaspal S Kooner, Florian Kronenberg, Brigitte Kühnel, Christine Ladd-Acosta, Terho Lehtimäki, Lars Lind, Dan Liu, Donald M Lloyd-Jones, Stefan Lorkowski, Ake T Lu, Riccardo E Marioni, Winfried März, Daniel L Mccartney, Karlijn A C Meeks, Lili Milani, Pashupati P Mishra, Matthias Nauck, Christoph Nowak, Annette Peters, Holger Prokisch, Bruce M Psaty, Olli T Raitakari, Scott M Ratliff, Alex P Reiner, Ben Schöttker, Joel Schwartz, Sanaz Sedaghat, Jennifer A Smith, Nona Sotoodehnia, Hannah R Stocker, Silvia Stringhini, Johan Sundström, Brenton R Swenson, Joyce B J Van Meurs, Jana V Van Vliet-Ostaptchouk, Andrea Venema, Uwe Völker, Juliane Winkelmann, Bruce H R Wolffenbuttel, Wei Zhao, Yinan Zheng, Marie Loh, Harold Snieder, Melanie Waldenberger, Daniel Levy, Shreeram Akilesh, Owen M Woodward, Katalin Susztak, Alexander Teumer, Anna Köttgen

Faculty, Staff and Student Publications

Elevated serum urate levels, a complex trait and major risk factor for incident gout, are correlated with cardiometabolic traits via incompletely understood mechanisms. DNA methylation in whole blood captures genetic and environmental influences and is assessed in transethnic meta-analysis of epigenome-wide association studies (EWAS) of serum urate (discovery, n = 12,474, replication, n = 5522). The 100 replicated, epigenome-wide significant (p < 1.1E-7) CpGs explain 11.6% of the serum urate variance. At SLC2A9, the serum urate locus with the largest effect in genome-wide association studies (GWAS), five CpGs are associated with SLC2A9 gene expression. Four CpGs at SLC2A9 have significant causal effects on serum urate levels and/or gout, and two of these partly mediate the effects of urate-associated GWAS variants. In other genes, including SLC7A11 and PHGDH, 17 urate-associated CpGs are associated with conditions defining metabolic syndrome, suggesting that these CpGs may represent a blood DNA methylation signature of cardiometabolic risk factors. This study demonstrates that EWAS can provide new insights into GWAS loci and the correlation of serum urate with other complex traits.

Hedgehog-Interacting Protein Is A Multimodal Antagonist Of Hedgehog Signalling, Samuel C Griffiths, Rebekka A Schwab, Kamel El Omari, Benjamin Bishop, Ellen J Iverson, Tomas Malinauskas, Ramin Dubey, Mingxing Qian, Douglas F Covey, Robert J C Gilbert, Rajat Rohatgi, Christian Siebold

Open Access Publications

Hedgehog (HH) morphogen signalling, crucial for cell growth and tissue patterning in animals, is initiated by the binding of dually lipidated HH ligands to cell surface receptors. Hedgehog-Interacting Protein (HHIP), the only reported secreted inhibitor of Sonic Hedgehog (SHH) signalling, binds directly to SHH with high nanomolar affinity, sequestering SHH. Here, we report the structure of the HHIP N-terminal domain (HHIP-N) in complex with a glycosaminoglycan (GAG). HHIP-N displays a unique bipartite fold with a GAG-binding domain alongside a Cysteine Rich Domain (CRD). We show that HHIP-N is required to convey full HHIP inhibitory function, likely by interacting with the …