Distributing Data and Analysis Software Containers For Better Data Sharing in Clinical Research

Introduction: Data sharing in clinical research is critical for increasing knowledge discovery. Data and software tools should be FAIR: Findable, Accessible, Inter-operable and Re-usable. Many bottlenecks exist in the process of a clinical investigator using shared data including data acquisition and statistical analysis. The objective of this project is to develop a structure for sharing data and providing rapid automated statistical analysis through creation of a pre-packaged, open-source software container. Methods: We use the open source software container technologies VirtualBox and Vagrant to create a template for sharing clinical data and analysis scripts as a single container. We use a timer to record the time necessary to setup and initialize the software container and view the results. Results: We have created a template for sharing data and analysis scripts together using open source software container technologies VirtualBox and Vagrant. We found the time needed to initialize the container to be 5 minutes and 36 seconds for a macOS-based machine and 7 minutes and 2 seconds for a Windows-based machine. Containers can be downloaded and executed from any Mac or Windows computer allowing both the reuse of and interaction with the data. This greatly reduces the time and effort needed to obtain and analyze clinical data. Conclusion: Reducing the time and effort needed to obtain and analyze clinical data increases the time available for data exploration and the discovery of new knowledge. This can be effectively achieved using software containers and virtualization

Multistate Hepatitis A Outbreak: Vaccination of Food Service Workers as Part of the Kentucky Outbreak Response

Background: In August 2017, a local outbreak of Hepatitis A was identified among homeless individuals in Louisville, Kentucky. This marked the first cases in what has now become recognized as the largest Hepatitis A outbreak in the US. When infection was identified in a Food Service Worker (FSW), vaccination efforts were expanded to target this group. Objective: The purpose of this study was to describe: 1) the processes used to provide access to Hepatitis A vaccine for FSWs, 2) results from the immunization activities, and 3) lessons learned from the outcomes. Methods: Through a partnership between the Louisville Metro Department of Public Health and Wellness (LMDPHW) and the University of Louisville Division of Infectious Diseases, a novel approach to vaccination was implemented. Access to vaccine was provided via on-site immunization in 66 restaurants and subsequent availability in a pop-up vaccination clinic. Data were collected using the LMDPHW data collection form and included demographics, risk factors for Hepatitis A, and vaccine documentation. Results for those vaccinated March-December 2018 were analyzed using descriptive statistics. Results: On-site vaccination was provided to 1337 FSW at 66 restaurants during the seven (7) week period from March 28-May 15, 2018. This process involved a team of 42 including Advanced Practice Registered Nurses, Registered and Licensed Practical Nurses, Physicians, and UL team members. During the 35 weeks the walk-in clinic has been in operation (May 16-December 31, 2018), 3068 additional FSW were vaccinated for a total of 4405 FSWs vaccinated as part of the outbreak response. Critical partners included the Kentucky Restaurant Association and the Kentucky Nurses Association. Conclusions: This study demonstrated a successful model for vaccination of a novel population during an infectious disease outbreak and the importance of expanding partnership networks to ensure success. The outcomes emphasized the importance of the resources available in the academic community for reliable and consistent public health emergency response

Refugee-Centered Medical Home:A New Approach to Care at the University of Louisville Global Health Center

Refugees arrive to the United States with a full spectrum of health conditions, many of which involve intense case management requiring significant financial investments and use of healthcare resources. Kentucky receives more than 3,000 new refugees each year and ranked 10th in the nation for numbers of new arrivals resettled during 2015. These refugees arrive from diverse countries representing different cultures and speaking different languages. In addition, they arrive with diverse health conditions and medical needs. The aims of this paper are to share experiences from the University of Louisville Global Health Center regarding conceptualization, implementation and evaluation of a new care model. This model focuses on the complexities of caring for refugees from diverse populations and backgrounds. The foundation for this model aligns with the patient-centered medical home approach outlined by the Agency for Healthcare Research and Quality. Recognizing the need for a new paradigm for care, a refugee-centered medical home model was designed and implemented as an ideal approach

Antimicrobial Stewardship in Hospitalized Patients with Respiratory Infections: Ten-Year Experience from the Robley Rex Louisville VA Medical Center

Rationale: Antibiotic stewardship has been defined as coordinated interventions designed to improve and measure the appropriate use of antibiotic agents. Respiratory infections are the most common infectious reason for hospitalization in the United States. Therefore, one could extrapolate that respiratory infections are then also the most common reason for hospital antibiotic use and possess the highest potential for hospital antibiotic misuse. The primary objective of this article was to evaluate the role of antimicrobial stewardship on improving antibiotic use for respiratory infections in hospitalized patients on intravenous (IV) antibiotics at the Robley Rex Louisville VAMC over a 10-year period. Methods: This was a retrospective review of the Robley Rex Louisville VAMC ASP Switch Therapy and Antimicrobial Review database. The study included all Robley Rex Louisville VAMC patients admitted to the hospital and placed on IV antibiotics between January 1st 2007 and December 31st 2016. Results: Recommendations from an antimicrobial stewardship team (AST) improve hospital IV antibiotic use in respiratory infections to a level above 90%. Conclusion: AST recommendations regarding antibiotic use for respiratory infections improve compliance with hospital guidelines. There is an ongoing role for antimicrobial stewardship programs overtime

Healthcare Workers Hospitalized with COVID-19: Outcomes from the Burden of COVID-19 study at the University of Louisville Center of Excellence for Research in Infectious Diseases [CERID]

Introduction: On March 6, 2020, the current ongoing pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) also known as COVID-19 reached the commonwealth of Kentucky. Within days the first cases of infection and hospitalization were identified among healthcare workers (HCW) in Kentucky, other states in the U.S., and around the world. There is little information available regarding the impact of COVID-19 on the HCW population within this area. The objective of this study is to describe the baseline characteristics of hospitalized HCWs infected with COVID-19. Methods: Data collection was performed as part of a retrospective study of patients hospitalized with COVID-19 in any of nine acute care hospitals in Louisville. COVID-19 infection was confirmed using Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR). Descriptive statistics were performed on clinical and epidemiological characteristics of hospitalized patients with COVID-19 who had indicated healthcare as their occupation. Results: Of the 700 adults hospitalized with COVID-19 from March 7 through July 1, 2020, 23 were HCWs. The mean age was 51 years and 78% were female. The majority of hospitalized HCWs had comorbidities including obesity (70%), hypertension (57%), hyperlipidemia (35%) and diabetes (26%). Common symptoms reported were fever (70%), dyspnea (78%), cough (78%) and fatigue (57%). Nine HCWs (39%) were admitted to the intensive care unit (ICU) and 6 (26%) developed acute respiratory distress syndrome (ARDS). Two (9%) patients developed a new, serious arrhythmia, two sustained cardiac arrest (9%), and two (9%) died in-hospital. Conclusions: Older adult HCWs with underlying health conditions such as obesity and hypertension were more likely to be hospitalized and have severe in-hospital complications. One HCW death due to COVID-19 was identified in this small population. These findings can help to identify and strengthen approaches to protect HCWs from SARS-CoV-2 infection and from long term effects of COVID-19

Photoreception and transcriptomic response to light during early development of a teleost with a life cycle tightly controlled by seasonal changes in photoperiod

Light cues vary along the axis of periodicity, intensity and spectrum and perception of light is dependent on the photoreceptive capacity encoded within the genome and the opsins expressed. A global approach was taken to analyze the photoreceptive capacity and the effect of differing light conditions on a developing teleost prior to first feeding. The transcriptomes of embryos and alevins of Atlantic salmon (Salmo salar) exposed to different light conditions were analyzed, including a developmental series and a circadian profile. The results showed that genes mediating nonvisual photoreception are present prior to hatching when the retina is poorly differentiated. The clock genes were expressed early, but the circadian profile showed that only two clock genes were significantly cycling before first feeding. Few genes were differentially expressed between day and night within a light condition; however, many genes were significantly different between light conditions, indicating that light environment has an impact on the transcriptome during early development. Comparing the transcriptome data from constant conditions to periodicity of white light or different colors revealed overrepresentation of genes related to photoreception, eye development, muscle contraction, degradation of metabolites and cell cycle among others, and in constant light, several clock genes were upregulated. In constant white light and periodicity of green light, genes associated with DNA replication, chromatin remodeling, cell division and DNA repair were downregulated. The study implies a direct influence of light conditions on the transcriptome profile at early developmental stages, by a complex photoreceptive system where few clock genes are cycling.publishedVersio

Level of Recall Bias Regarding Pneumococcal Vaccination History among Adults Hospitalized with Community-Acquired Pneumonia: Results from the University of Louisville Pneumonia Study

Background: Recall bias is likely to occur in vaccine effectiveness studies using self-reported vaccination history. The validity of patient-reported vaccination status for adults is not well defined. The objective of this study was to evaluate the validity of self-reported pneumococcal vaccination history among patients hospitalized with community-acquired pneumonia (CAP). Methods: Prospective ancillary study of a population-based observational study of hospitalized patients with CAP in the city of Louisville. To be included in the analysis, patients had to (i) be reached by phone 30-days after discharge from the hospital and (ii) report that they remembered whether or not they received a pneumococcal vaccine in the past five years. The vaccination history was classified as 1) Subjective: patient recollection, or 2) Objective: vaccination records from insurance companies or primary care physicians. Results: A total of 2,787 patients who recalled their vaccination history were included in the analysis. Subjective vaccination history was documented to be inaccurate in 1,023 (37%) patients. Conclusions: Our study indicates that in adult patients, self-reported data regarding pneumococcal vaccination is likely to be inaccurate in one out of three patients. This level of recall bias may incorporate a fatal flaw in vaccine effectiveness studies

Using Y-chromosome capture enrichment to resolve haplogroup H2 shows new evidence for a two-Path Neolithic expansion to Western Europe

Uniparentally-inherited markers on mitochondrial DNA (mtDNA) and the non-recombining regions of the Y chromosome (NRY), have been used for the past 30 years to investigate the history of humans from a maternal and paternal perspective.Researchers have preferred mtDNA due to its abundance in the cells, and comparatively high substitution rate. Conversely, the NRY is less susceptible to back mutations and saturation, and is potentially more informative than mtDNA owing to its longer sequence length. However, due to comparatively poor NRY coverage via shotgun sequencing, and the relatively low and biased representation of Y-chromosome variants on capture arrays such as the 1240K, ancient DNA studies often fail to utilize the unique perspective that the NRY can yield.Here we introduce a new DNA enrichment assay, coined YMCA (Y-mappable capture assay), that targets the “mappable” regions of the NRY. We show that compared to low-coverage shotgun sequencing and 1240K capture, YMCA significantly improves the coverage and number of sites hit on the NRY, increasing the number of Y-haplogroup informative SNPs, and allowing for the identification of previously undiscovered variants.To illustrate the power of YMCA, we show that the analysis of ancient Y-chromosome lineages can help to resolve Y-chromosomal haplogroups. As a case study, we focus on H2, a haplogroup associated with a critical event in European human history: the Neolithic transition. By disentangling the evolutionary history of this haplogroup, we further elucidate the two separate paths by which early farmers expanded from Anatolia and the Near East to western Europe.Competing Interest StatementThe authors have declared no competing interest.Introduction Results and Discussion - Validating the performance of YMCA - Application of YMCA to YHG H2 as a case study - Identifying diagnostic SNPs for improved YHG H2 resolution Discussion Materials and Methods - Data - Contamination quality filtering - Method of Y Haplogroup Assignment - Comparing the Performance of our Y-capture Array Phylogenetic Tree Reconstructio

Modification of EGF-Like Module 1 of Thrombospondin-1, an Animal Extracellular Protein, by O-Linked N-Acetylglucosamine

Thrombospondin-1 (TSP-1) is known to be subject to three unusual carbohydrate modifications: C-mannosylation, O-fucosylation, and O-glucosylation. We now describe a fourth: O-β-N-acetylglucosaminylation. Previously, O-β-N-acetylglucosamine (O-β-GlcNAc) was found on a threonine in the loop between the fifth and sixth cysteines of the 20th epidermal growth factor (EGF)-like module of Drosophila Notch. A BLAST search based on the Drosophila Notch loop sequence identified a number of human EGF-like modules that contain a similar sequence, including EGF-like module 1 of TSP-1 and its homolog, TSP-2. TSP-1, which has a potentially modifiable serine in the loop, reacted in immuno-blots with the CTD110.6 anti-O-GlcNAc antibody. Antibody reactivity was diminished by treatment of TSP-1 with β-N-acetylhexosaminidase. TSP-2, which lacks a potentially modifiable serine/threonine in the loop, did not react with CTD110.6. Analysis of tandem modules of TSP-1 localized reactivity of CTD110.6 to EGF-like module 1. Top-down mass spectrometric analysis of EGF-like module 1 demonstrated the expected modifications with glucose (+162 Da) and xylose (+132 Da) separately from modification with N-acetyl hexosamine (+203 Da). Mass spectrometric sequence analysis localized the +203-Da modification to Ser580 in the sequence 575CPPGYSGNGIQC586. These results demonstrate that O-β-N-acetylglucosaminylation can occur on secreted extracellular matrix proteins as well as on cell surface proteins