Medicine and Health Sciences Commons^™

Develop A Rotational Robust Optimized Spot-Scanning Proton Arc (Sparc) Algorithm, Shupeng Chang, Gang Liu, Lewei Zhao, Weili Zheng, An Qin, Di Yan, Xiaoqiang Li, Xuanfeng Ding

Conference Presentation Abstracts

No abstract provided.

Clinical, Neuroimaging, And Molecular Spectrum Of Tecpr2-Associated Hereditary Sensory And Autonomic Neuropathy With Intellectual Disability, Sonja Neuser, Barbara Brechmann, Gali Heimer, Ines Brösse, Susanna Schubert, Lauren O'Grady, Michael Zech, Siddharth Srivastava, Shahnaz Ibrahim, Fatima Khan

Department of Paediatrics and Child Health

Bi-allelic TECPR2 variants have been associated with a complex syndrome with features of both a neurodevelopmental and neurodegenerative disorder. Here, we provide a comprehensive clinical description and variant interpretation framework for this genetic locus. Through international collaboration, we identified 17 individuals from 15 families with bi-allelic TECPR2-variants. We systemically reviewed clinical and molecular data from this cohort and 11 cases previously reported. Phenotypes were standardized using Human Phenotype Ontology terms. A cross-sectional analysis revealed global developmental delay/intellectual disability, muscular hypotonia, ataxia, hyporeflexia, respiratory infections, and central/nocturnal hypopnea as core manifestations. A review of brain magnetic resonance imaging scans demonstrated a …

Evaluating Motor Performance With The Bruininks-Oseretsky Test Of Motor Proficiency In Impoverished Pakistani Children, Zehra Habib Hasan, Fariha Shaheen, Arjumand Rizvi, Jelena Obradovic, Aisha Khan Yousafzai

Department of Paediatrics and Child Health

Objective: To evaluate the sensitivity of the modified Brief Form of Bruininks Oseretsky Test in identifying motor differences secondary to malnutrition and poverty.
Methods: This longitudinal cohort study was conducted at Nowshero Feroze, Sindh from 2013 to 2014 and comprised data drawn from children who participated in a randomised controlled trial, that assessed responsive stimulation and nutrition interventions in the first two years of life. Outcome measures included motor development assessed using Brief Form of Bruininks Oseretsky Test, child anthropometry and household economic and demographic information. Data was analysed using SPSS 15 and STATA 12.
Results: Of the 1058 children, …

Providing Palliative And Hospice Care To Children, Adolescents And Young Adults With Cancer, Kimberly A. Pyke-Grimm, Beth Fisher, Amy Haskamp, Cynthia J. Bell, Amy Rose Newman

College of Nursing Faculty Research and Publications

Objectives

To describe palliative, concurrent, and hospice care in pediatric oncology in the United States (US), we present a clinical scenario illustrating palliative and hospice care, including eligibility for concurrent care, insurance coverage and billing, barriers to accessing quality pediatric palliative and hospice care, and implications for oncology nursing practice.

Data Sources

Peer-reviewed articles, clinical practice guidelines, professional organizations, and expert clinical opinion examining pediatric oncology, palliative care, and hospice care.

Conclusion

Understanding the goals of palliative and hospice care and the differences between them is important in providing holistic, goal-directed care.

Implications for Nursing Practice

Oncology nurses play …

Mental Health Outcomes Of Various Types Of Fear Among University Students Who Have An Undocumented Legal Status During The Donald Trump Presidency, Liliana Campos

Doctoral Dissertations

Having an undocumented legal status is a risk factor for mental health conditions such as depression and anxiety among university students. Much of the literature on the experiences of university students who hold an undocumented legal status has primarily focused on better understanding the educational, social, financial, and legal challenges among undergraduate students. The literature has addressed how some of these difficulties impact components of their social and mental health wellness. Yet, there is still a dearth of research focused on further understanding the experiences of students who hold an undocumented legal status from a psychological perspective, and specifically, with …

Toxoplasma Gondii, Suicidal Behavior, And Intermediate Phenotypes For Suicidal Behavior, Teodor T. Postolache, Abhishek Wadhawan, Dan Rujescu, Andrew J. Hoisington, Aline Dagdag, Enrique Baca-Garcia, Christopher A. Lowry, Olaoluwa O. Okusaga, Lisa A. Brenner

Faculty Publications

Within the general literature on infections and suicidal behavior, studies on Toxoplasma gondii ( T. gondii ) occupy a central position. This is related to the parasite's neurotropism, high prevalence of chronic infection, as well as specific and non-specific behavioral alterations in rodents that lead to increased risk taking, which are recapitulated in humans by T. gondii's associations with suicidal behavior, as well as trait impulsivity and aggression, mental illness and traffic accidents. This paper is a detailed review of the associations between T. gondii serology and suicidal behavior, a field of study that started 15 years ago with our …

Socioeconomic And Demographic Correlates Of Nonenrolment Onto The National Health Insurance Scheme Among Children In Ghana: Insight From The 2017/18 Multiple Indicator Cluster Survey, Pascal Agbadi, Joshua Okyere, Alberta Lomotey, Henry Ofori Duah, Abdul-Aziz Seidu, Bright Opoku Ahinkorah

College of Nursing Faculty Research and Publications

The goal of Ghana’s health insurance scheme is to achieve universal coverage. Despite NHIS’ benefits to children, not all children in Ghana are covered. This study investigates the sociodemographic covariates of nonenrolment onto the national health insurance scheme among children in Ghana. We used the child dataset of the 2017/18 Ghana Multiple Indicator Cluster Survey (G-MICS). We used STATA version 14 for the data analyses. We described each study variable using frequency and percentages. We used Poisson regression to estimate crude and adjusted prevalence ratios of the relationship between the covariates and the outcome variable. Approxi­ mately 57% of children …

Correlates Of Blood Pressure And Blood Glucose Screenings In Cameroon: Insights From The 2018 Demographic And Health Survey, Precious Adade Duodu, Pascal Agbadi, Henry Ofori Duah, Ernest Darkwah, Jerry John Nutor

College of Nursing Faculty Research and Publications

Background

Hypertension and diabetes, two major risk factors for cardiometabolic diseases, are associated with high morbidity and mortality rates. Early detection through screening can initiate early treatment to reduce adverse outcomes. The current study sought to investigate the correlates of blood pressure and blood glucose screenings in Cameroon.

Methods

We used secondary data from the 2018 Cameroon Demographic and Health Survey. Adjusting for a complex sample design, we performed multivariate prevalence ratio estimates of the blood pressure and blood glucose screenings.

Results

Approximately 60% and 30% of Cameroonians had undergone blood pressure and blood glucose screenings, respectively. More females (68%) …

Ethics & Pricing In The Pharmaceutical Industry, Ayo-Oluwa Laleye

Student Research

During the final weeks of Professor Dan Gurnon’s CHEM 343 class, students are given the opportunity to present a topic that intersects with the biochemistry knowledge learned over the course of their semester. For my presentation, I chose to explore a specific ethical and moral issue of drug pricing in the bio-pharmaceutical industry. This presentation dives deep into the metabolic functional pathways of Daraprim, a WHO essential medicine and the scandal that surrounds the pricing of the medication. The cost of Daraprim rose from $13.50 to $750 per pill, a 5455% increase for a medication that costs less than $2 …

Randomized Trial Of The Efficacy And Safety Of Berotralstat (Bcx7353) As An Oral Prophylactic Therapy For Hereditary Angioedema: Results Of Apex-2 Through 48 Weeks (Part 2), H James Wedner, Et Al.

2020-Current year OA Pubs

BACKGROUND: Berotralstat (BCX7353) is a recently approved, oral, once-daily kallikrein inhibitor for hereditary angioedema (HAE) prophylaxis. In the APeX-2 trial, berotralstat reduced HAE attack rates over 24 weeks, with a favorable safety and tolerability profile.

OBJECTIVE: Evaluate berotralstat safety, tolerability, and effectiveness over 48 weeks.

METHODS: APeX-2 is a phase 3, parallel-group, multicenter trial (NCT03485911) in patients with HAE due to C1 esterase inhibitor deficiency. Part 1 was double-blind and placebo-controlled, with patients randomized to 24 weeks of berotralstat 150 mg, 110 mg, or placebo. In part 2, patients continued berotralstat the same dose or, if initially randomized to placebo, …

Clinical Epigenomics: Genome-Wide Dna Methylation Analysis For The Diagnosis Of Mendelian Disorders, Bekim Sadikovic, Jorge L Granadillo, Et Al.

2020-Current year OA Pubs

PURPOSE: We describe the clinical implementation of genome-wide DNA methylation analysis in rare disorders across the EpiSign diagnostic laboratory network and the assessment of results and clinical impact in the first subjects tested.

METHODS: We outline the logistics and data flow between an integrated network of clinical diagnostics laboratories in Europe, the United States, and Canada. We describe the clinical validation of EpiSign using 211 specimens and assess the test performance and diagnostic yield in the first 207 subjects tested involving two patient subgroups: the targeted cohort (subjects with previous ambiguous/inconclusive genetic findings including genetic variants of unknown clinical significance) …

Commonalities Across Computational Workflows For Uncovering Explanatory Variants In Undiagnosed Cases, Shilpa Nadimpalli Kobren, Dustin Baldridge, Daniel J Wegner, Alexander J Paul, Et Al.

2020-Current year OA Pubs

PURPOSE: Genomic sequencing has become an increasingly powerful and relevant tool to be leveraged for the discovery of genetic aberrations underlying rare, Mendelian conditions. Although the computational tools incorporated into diagnostic workflows for this task are continually evolving and improving, we nevertheless sought to investigate commonalities across sequencing processing workflows to reveal consensus and standard practice tools and highlight exploratory analyses where technical and theoretical method improvements would be most impactful.

METHODS: We collected details regarding the computational approaches used by a genetic testing laboratory and 11 clinical research sites in the United States participating in the Undiagnosed Diseases Network …

A Peptide-Based Checkpoint Immunomodulator Alleviates Immune Dysfunction In Murine Polymicrobial Sepsis, Timothy W Phares, Vinayaka Kotraiah, Chun-Shiang Chung, Jacqueline Unsinger, Monty Mazer, Kenneth E. Remy, Cecille D. Browne, Peter Buontempo, Marc Mansour, James Pannucci, Alfred Ayala, Richard S. Hotchkiss, Gabriel M. Gutierrez

2020-Current year OA Pubs

Sepsis-induced immunosuppression involves both innate and adaptive immunity and is associated with the increased expression of checkpoint inhibitors, such as programmed cell-death protein 1 (PD-1). The expression of PD-1 is associated with poor outcomes in septic patients, and in models of sepsis, blocking PD-1 or its ligands with antibodies increased survival and alleviated immune suppression. While inhibitory antibodies are effective, they can lead to immune-related adverse events (irAEs), in part due to continual blockade of the PD-1 pathway, resulting in hyperactivation of the immune response. Peptide-based therapeutics are an alternative drug modality that provide a rapid pharmacokinetic profile, reducing the …

Sars-Cov-2 Detection Among International Air Travellers To Ghana During Mandatory Quarantine, Bright Adu, Joseph K H Bonney, John K Odoom, Evelyn Y A Bonney, Evangeline Obodai, Ivy A Asante, James Aboagye, Mildred A Adusei-Poku, Lawrence Lartey, Ernest K Asiedu, William K Ampofo, George B Kyei

2020-Current year OA Pubs

OBJECTIVES: To determine the prevalence of SARS-CoV-2 detection among international travellers to Ghana during mandatory quarantine.

DESIGN: A retrospective cross-sectional study.

SETTING: Air travellers to Ghana on 21

PARTICIPANTS: On 21

MAIN OUTCOME MEASURE: Positivity for SARS-CoV-2 by polymerase chain reaction.

RESULTS: The initial testing at the beginning of quarantine found 79 (7.7%) individuals to be positive for SARS-CoV-2. In the exit screening after 12 to 13 days of quarantine, it was discovered that 26 of those who tested negative for SARS-CoV-2 in the initial screening subsequently tested positive.

CONCLUSIONS: Ghana likely averted an early community spread of COVID-19 through …

Outcomes And Risk Factors Associated With Sars-Cov-2 Infection In A North American Registry Of Patients With Multiple Sclerosis, Amber Salter, Robert J Fox, Scott D Newsome, June Halper, David K B Li, Pamela Kanellis, Kathleen Costello, Bruce Bebo, Kottil Rammohan, Gary R Cutter, Anne H Cross

2020-Current year OA Pubs

Importance: Emergence of SARS-CoV-2 causing COVID-19 prompted the need to gather information on clinical outcomes and risk factors associated with morbidity and mortality in patients with multiple sclerosis (MS) and concomitant SARS-CoV-2 infections.

Objective: To examine outcomes and risk factors associated with COVID-19 clinical severity in a large, diverse cohort of North American patients with MS.

Design, Setting, and Participants: This analysis used deidentified, cross-sectional data on patients with MS and SARS-CoV-2 infection reported by health care professionals in North American academic and community practices between April 1, 2020, and December 12, 2020, in the COVID-19 Infections in MS Registry. …

Transfer Transcriptomic Signatures For Infectious Diseases, Julia Di Iulio, Istvan Bartha, Roberto Spreafico, Herbert W Virgin, Amalio Telenti

2020-Current year OA Pubs

The modulation of the transcriptome is among the earliest responses to infection. However, defining the transcriptomic signatures of disease is challenging because logistic, technical, and cost factors limit the size and representativeness of samples in clinical studies. These limitations lead to a poor performance of signatures when applied to new datasets. Although the study focuses on infection, the central hypothesis of the work is the generalization of sets of signatures across diseases. We use a machine learning approach to identify common elements in datasets and then test empirically whether they are informative about a second dataset from a disease or …

Brain-Responsive Neurostimulation For The Treatment Of Adults With Epilepsy In Tuberous Sclerosis Complex: A Case Series, Danielle S Mcdermott, Emily A Mirro, Kirsten Fetrow, David E Burdette, Stephanie Chen, Jennifer Hopp, Todd Masel, Emily A Johnson, Felicia M K Elefant, Scheherazade Le, Sanjay E Patra, Mesha-Gay Brown, Zulfi Haneef

2020-Current year OA Pubs

OBJECTIVE: Tuberous sclerosis complex (TSC) is a genetic disorder primarily characterized by the development of multisystem benign tumors. Epilepsy is the most common neurologic manifestation, affecting 80%-90% of TSC patients. The diffuse structural brain abnormalities and the multifocal nature of epilepsy in TSC pose diagnostic challenges when evaluating patients for epilepsy surgery.

METHODS: We retrospectively reviewed the safety experience and efficacy outcomes of five adult TSC patients who were treated with direct brain-responsive neurostimulation (RNS System, NeuroPace, Inc).

RESULTS: The average follow-up duration was 20 months. All five patients were responders (≥50% disabling seizure reduction) at last follow-up. The median …

Multiparametric Early Detection And Prediction Of Cardiotoxicity Using Myocardial Strain, T1 And T2 Mapping, And Biochemical Markers: A Longitudinal Cardiac Resonance Imaging Study During 2 Years Of Follow-Up, Sorin Giusca, Grigorios Korosoglou, Moritz Montenbruck, Blaž Geršak, Arne Kristian Schwarz, Sebastian Esch, Sebastian Kelle, Pia Wülfing, Susan Dent, Daniel Lenihan, Henning Steen

2020-Current year OA Pubs

BACKGROUND: Our goal was to evaluate the ability of cardiovascular magnetic resonance for detecting and predicting cardiac dysfunction in patients receiving cancer therapy. Left ventricular ejection fraction, global and regional strain utilizing fast-strain-encoded, T1 and T2 mapping, and cardiac biomarkers (troponin and BNP [brain natriuretic peptide]) were analyzed.

METHODS: Sixty-one patients (47 with breast cancer, 11 with non-Hodgkin lymphoma, and 3 with Hodgkin lymphoma) underwent cardiovascular magnetic resonance scans at baseline and at regular intervals during 2 years of follow-up. The percentage of all left ventricular myocardial segments with strain ≤-17% (normal myocardium [%]) was analyzed. Clinical cardiotoxicity (CTX) and …

Addressing Cancer Survivors' Cardiovascular Health Using The Automated Heart Health Assessment (Ah-Ha) Ehr Tool: Initial Protocol And Modifications To Address Covid-19 Challenges, Randi E Foraker, Eleanor C Davidson, Emily V Dressler, Brian J Wells, Simon Craddock Lee, Heidi D Klepin, Karen M Winkfield, W Gregory Hundley, Philip R O Payne, Albert M Lai, Glenn J Lesser, Kathryn E Weaver

2020-Current year OA Pubs

BACKGROUND: The purpose of this paper is to describe the Automated Heart-Health Assessment (AH-HA) study protocol, which demonstrates an agile approach to cancer care delivery research. This study aims to assess the effect of a clinical decision support tool for cancer survivors on cardiovascular health (CVH) discussions, referrals, completed visits with primary care providers and cardiologists, and control of modifiable CVH factors and behaviors. The COVID-19 pandemic has caused widespread disruption to clinical trial accrual and operations. Studies conducted with potentially vulnerable populations, including cancer survivors, must shift towards virtual consent, data collection, and study visits to reduce risk for …

The Azithromycin To Prevent Wheezing Following Severe Rsv Bronchiolitis-Ii Clinical Trial: Rationale, Study Design, Methods, And Characteristics Of Study Population, Mythili Srinivasan, Leonard B Bacharier, Charles W Goss, Yanjiao Zhou, Jonathan Boomer, Sarah Bram, Dana Burgdorf, Carey-Ann Burnham, Timothy Casper, Mario Castro, Andrea Coverstone, Matthew Haslam, Watcharoot Kanchongkittiphon, Cadence Kuklinski, Qinghua Lian, Kenneth Schechtman, Gregory A Storch, Kelly True, Meghan A Wallace, Huiqing Yin-Declue, Elizabeth Ahrens, Jinli Wang, Avraham Beigelman

2020-Current year OA Pubs

Severe respiratory syncytial virus (RSV) bronchiolitis in early life is a significant risk factor for future recurrent wheeze (RW) and asthma. The goal of the Azithromycin to Prevent Wheezing following severe RSV bronchiolitis II (APW-RSV II) clinical trial is to evaluate if azithromycin treatment in infants hospitalized with RSV bronchiolitis reduces the occurrence of RW during the preschool years. The APW-RSV II clinical trial is a double-blind, placebo-controlled, parallel-group, randomized trial, including otherwise healthy participants, ages 30 days-18 months, who are hospitalized due to RSV bronchiolitis. The study includes an active randomized treatment phase with azithromycin or placebo for 2 …

Evaluation Of Serum-Derived Bovine Immunoglobulin Protein Isolate In Subjects With Decompensated Cirrhosis With Ascites, Matthew J. Stotts, Amanda Cheung, Muhammad B. Hammami, David J. Westrich Jr., Eric Anderson, Lauren Counts, Alex S. Befeler, Adrian M. Di Bisceglie, Charlene Prather

2020-Current year OA Pubs

Background Bacterial translocation plays a pivotal role in the natural course of cirrhosis and its complications. Serum-derived bovine immunoglobulin (SBI) is an oral medical food that has been shown to both reduce inflammation in the intestines and neutralize bacteria. It represents a unique intervention that has not been studied in this population. Methodology We conducted a prospective open-label trial with an eight-week treatment phase of SBI. Individuals were assessed using lactulose breath testing, serum markers for enterocyte damage and bacterial translocation, and the Chronic Liver Disease Questionnaire (CLDQ) prior to and after completion of the treatment phase. Results We evaluated …

Malda, Accelerating Malaria Drug Discovery, Tuo Yang, Eva S. Istvan, Daniel E. Goldberg, Et Al.

2020-Current year OA Pubs

The Malaria Drug Accelerator (MalDA) is a consortium of 15 leading scientific laboratories. The aim of MalDA is to improve and accelerate the early antimalarial drug discovery process by identifying new, essential, druggable targets. In addition, it seeks to produce early lead inhibitors that may be advanced into drug candidates suitable for preclinical development and subsequent clinical testing in humans. By sharing resources, including expertise, knowledge, materials, and reagents, the consortium strives to eliminate the structural barriers often encountered in the drug discovery process. Here we discuss the mission of the consortium and its scientific achievements, including the identification of …

A Carrier Without Sympathy, Mishal Ali

Student Research

This paper talks about the series of events that happened before and after Mary Mallon, more commonly and widely known as Typhoid Mary, was officially identified as the first asymptomatic and healthy carrier of typhoid. The paper highlights the ways the authorities and health officials dealt with Mary Mallon with respect to her intersectional identities of gender, race, class, and immigration status. It briefly reflects on some of the literary pieces surrounding Typhoid Mary as supporting sources to explore and understand how communities react and approach such situations and the ways authorities handled unknown contagious diseases and critique how specific …

A Low-Cost Priapism Detumescence Simulator For Emergency Medicine Residents., Zach Hampton, Nickolas Meier, John Casey

Medical Education Articles

INTRODUCTION: Ischemic priapism is an emergent condition requiring immediate intervention. However, the incidence is estimated to be very low. Given the low incidence of this pathology, some emergency medicine residents do not have the opportunity to perform needle aspiration, the critical procedure to achieve detumescence. We sought to fill this void by creating low-cost, high-fidelity trainers for emergency medicine resident procedural competency.

METHODS: Using items obtained online and through our hospital's simulation department, we created a low-cost priapism trainer from previously described literature. Residents completed a lecture, lab, and short post-course survey regarding helpfulness, realism, prior procedure experience, and future …

Association Of Clinical Factors And Recent Anticancer Therapy With Covid-19 Severity Among Patients With Cancer: A Report From The Covid-19 And Cancer Consortium, P Grivas, K E Stockerl-Goldstein, A Y Zhou, Et Al.

2020-Current year OA Pubs

BACKGROUND: Patients with cancer may be at high risk of adverse outcomes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We analyzed a cohort of patients with cancer and coronavirus 2019 (COVID-19) reported to the COVID-19 and Cancer Consortium (CCC19) to identify prognostic clinical factors, including laboratory measurements and anticancer therapies.

PATIENTS AND METHODS: Patients with active or historical cancer and a laboratory-confirmed SARS-CoV-2 diagnosis recorded between 17 March and 18 November 2020 were included. The primary outcome was COVID-19 severity measured on an ordinal scale (uncomplicated, hospitalized, admitted to intensive care unit, mechanically ventilated, died within 30 days). …

Elevated Mrna Expression And Defective Processing Of Cathepsin D In Hela Cells Lacking The Mannose 6-Phosphate Pathway, Lin Liu, Balraj Doray

2020-Current year OA Pubs

Disruption of the mannose 6-phosphate (M-6-P) pathway in HeLa cells by inactivation of the GNPTAB gene, which encodes the α/β subunits of GlcNAc-1-phosphotransferase, results in missorting of newly synthesized lysosomal acid hydrolases to the cell culture media instead of transport to the endolysosomal system. We previously demonstrated that the majority of the lysosomal aspartyl protease, cathepsin D, is secreted in these GNPTAB

Isolated Volar Dislocation Of The Distal Radioulnar Joint Treated With Successful Closed Reduction., Matthew T Glazier, Hayden B Schuette, Benjamin A Schnee, Brian Skura, Craig Goubeaux

Surgery Articles

We report the case of A 34-year-old right-hand-dominant male who presented with an isolated left volar dislocation of the distal radioulnar joint (DRUJ) without any associated fractures. The patient had sustained the injury in an altercation in the evening prior to the presentation and had woken up the next morning with left wrist pain and restricted wrist motion. Closed reduction was successful under conscious sedation and the patient was treated conservatively with splint immobilization without needing operative intervention. This report highlights a rare injury pattern - an isolated volar DRUJ dislocation - that was successfully closed reduced, despite reports that …

Identifying The Lipidomic Effects Of A Rare Loss-Of-Function Deletion In Angptl3, Nicholas B. Blackburn, Peter J. Meikle, Juan M. Peralta, Satish Kumar, Ana C. Leandro, Melissa A. Bellinger, Michael Mahaney, Harald H. H. Goring, John L. Vandeberg, Sarah Williams-Blangero, David C. Glahn, Ravi Duggirala, John Blangero, Joanne E. Curran

School of Medicine Publications

Background: The identification and understanding of therapeutic targets for atherosclerotic cardiovascular disease is of fundamental importance given its global health and economic burden. Inhibition of ANGPTL3 (angiopoietin-like 3) has demonstrated a cardioprotective effect, showing promise for atherosclerotic cardiovascular disease treatment, and is currently the focus of ongoing clinical trials. Here, we assessed the genetic basis of variation in ANGPTL3 levels in the San Antonio Family Heart Study.

Methods: We assayed ANGPTL3 protein levels in ≈1000 Mexican Americans from extended pedigrees. By drawing upon existing plasma lipidome profiles and genomic data we conducted analyses to understand the genetic basis to variation …

Gwas Significance Thresholds For Deep Phenotyping Studies Can Depend Upon Minor Allele Frequencies And Sample Size, Huma Asif, Ney Alliey-Rodriguez, Sarah Keedy, Carol A. Tamminga, John A. Sweeney

School of Medicine Publications

An important issue affecting genome-wide association studies with deep phenotyping (multiple correlated phenotypes) is determining the suitable family-wise significance threshold. Straightforward family-wise correction (Bonferroni) of p < 0.05 for 4.3 million genotypes and 335 phenotypes would give a threshold of p < 3.46E−11. This would be too conservative because it assumes all tests are independent. The effective number of tests, both phenotypic and genotypic, must be adjusted for the correlations between them. Spectral decomposition of the phenotype matrix and LD-based correction of the number of tested SNPs are currently used to determine an effective number of tests. In this paper, we compare these calculated estimates with permutation-determined family-wise significance thresholds. Permutations are performed by shuffling individual IDs of the genotype vector for this dataset, to preserve correlation of phenotypes. Our results demonstrate that the permutation threshold is influenced by minor allele frequency (MAF) of the SNPs, and by the number of individuals tested. For the more common SNPs (MAF > 0.1), the permutation family-wise threshold was in close agreement with spectral decomposition methods. However, for less common SNPs (0.05 < MAF ≤ 0.1), the permutation threshold calculated over all SNPs was off by orders of magnitude. This applies to the number of individuals studied (here 777) but not to very much larger numbers. Based on these findings, we propose that the threshold to find a particular level of family-wise significance may need to be established using separate permutations of the actual data for several MAF bins.

Positional Installation Of Intranasal Corticosteroids In The Treatment Of Chronic Rhinosinusitis: A Systematic Review Of The Literature, Emily L Cummings, Scott N Fassas, Kevin J Sykes, Amy Sisson, Alexander G Chiu, Meha G Fox

Library Staff Publications

OBJECTIVES: First-line treatment of chronic rhinosinusitis includes topical corticosteroids aimed at decreasing inflammation of sinonasal mucosa. No guidelines exist regarding the effect of head position during administration of corticosteroids. We hypothesize certain positions enhance delivery to the paranasal sinuses, with further improvement in delivery after sinus surgery.

METHODS: A systematic review of the literature was conducted using Medline Ovid, Embase, Scopus, and Cochrane databases. All studies evaluating intranasal medications administered in 2 or more head positions were included. Study population, head position(s), method/volume of delivery, and outcome metrics were recorded.

RESULTS: Twenty-four studies compared head positions and their role in …