Digital Commons Network^™

Rotavirus-Induced Lipid Droplet Biogenesis Is Critical For Virus Replication, Jeanette M Criglar, Mary K Estes, Sue E Crawford

Faculty, Staff and Students Publications

A variety of pathogens, including viruses, bacteria and parasites, target cellular lipid droplets for their replication. Rotaviruses (RVs) infect the villous epithelium of the small intestine and are a major cause of acute gastroenteritis in infants and young children worldwide. RVs induce and require lipid droplets for the formation of viroplasms, sites of virus genome replication, and nascent particle assembly. Here we review the role of lipid droplets in RV replication. Inhibitors of fatty acid synthesis or chemicals that interfere with lipid droplet homeostasis decrease the number and size of viroplasms and the yield of infectious virus. We used a …

Decidualization Of Human Endometrial Stromal Cells Requires Steroid Receptor Coactivator-3, Vineet K Maurya, Maria M Szwarc, David M Lonard, William E Gibbons, San-Pin Wu, Bert W O'Malley, Francesco J Demayo, John P Lydon

Faculty, Staff and Students Publications

Steroid receptor coactivator-3 (SRC-3; also known as NCOA3 or AIB1) is a member of the multifunctional p160/SRC family of coactivators, which also includes SRC-1 and SRC-2. Clinical and cell-based studies as well as investigations on mice have demonstrated pivotal roles for each SRC in numerous physiological and pathophysiological contexts, underscoring their functional pleiotropy. We previously demonstrated the critical involvement of SRC-2 in murine embryo implantation as well as in human endometrial stromal cell (HESC) decidualization, a cellular transformation process required for trophoblast invasion and ultimately placentation. We show here that, like SRC-2, SRC-3 is expressed in the epithelial and stromal …

Nuclear Progesterone Receptor Expressed By The Cortical Thymic Epithelial Cells Dictates Thymus Involution In Murine Pregnancy, Soo Hyun Ahn, Sean L Nguyen, Tae Hoon Kim, Jae-Wook Jeong, Ripla Arora, John P Lydon, Margaret G Petroff

Faculty, Staff and Students Publications

Progesterone is a gonadal pro-gestational hormone that is absolutely necessary for the success of pregnancy. Most notable actions of progesterone are observed in the female reproductive organs, the uterus and the ovary. Acting through the nuclear progesterone receptor (PGR), progesterone prepares the endometrium for implantation of the embryo. Interestingly, the maternal thymus also is a known expressor of Pgr; its absence is associated with murine pregnancy complications. However, the localization of its expression and its functional importance were not known. Here, we used a transgenic dual fluorescent reporter mouse model and genetic deletion of Pgr in Foxn1+ thymic epithelial …

Stress-Associated Metabolites Vary With Both Season And Habitat Across Populations Of A Climate Sentinel Species, A. L. Whipple, C. Ray, J. Varner, J. N. Kitchens, A. A. Hove, J. A. Castillo Vardaro, J. L. Wilkening

Faculty Research, Scholarly, and Creative Activity

Relating physiological stress to habitat quality could refine conservation efforts. Habitat quality, which is often inferred from patch occupancy or demographic rates, might be measured in a more timely and nuanced way using metrics of physiological stress. To understand whether stress-associated hormones vary with metrics of habitat quality, we measured fecal glucocorticoid metabolite (FGM) levels in the American pika (Ochotona princeps), a small mammal with well-defined habitat (talus), which can vary in quality depending on the presence of subsurface ice features. In spring and fall 2018, we collected feces noninvasively from pika territories in taluses “with” or “without” subsurface ice …

Nav1.1 Is Essential For Proprioceptive Signaling And Motor Behaviors, Cyrrus M. Espino, Cheyanne M. Lewis, Serena Ortiz, Miloni S. Dalal, Snigdha Garlapalli, Kaylee M. Wells, Darik A. O'Neil, Katherine A. Wilkinson, Theanne N. Griffith

Faculty Research, Scholarly, and Creative Activity

The voltage-gated sodium channel (NaV), NaV1.1, is well-studied in the central nervous system; conversely, its contribution to peripheral sensory neuron function is more enigmatic. Here, we identify a new role for NaV1.1 in mammalian proprioception. RNAscope analysis and in vitro patch-clamp recordings in genetically identified mouse proprioceptors show ubiquitous channel expression and significant contributions to intrinsic excitability. Notably, genetic deletion of NaV1.1 in sensory neurons caused profound and visible motor coordination deficits in conditional knockout mice of both sexes, similar to conditional Piezo2-knockout animals, suggesting that this channel is a major contributor to sensory proprioceptive transmission. Ex vivo muscle afferent …

In-Vehicle Human Machine Interface: Investigating The Effects Of Tactile Displays On Information Presentation In Automated Vehicles, Kimberly D. Martinez, Gaojian Huang

Faculty Research, Scholarly, and Creative Activity

Background: Semi-autonomous vehicles still require human drivers to take over when the automated systems can no longer perform the driving task. Objective: The goal of this study was to design and test the effects of six meaningful tactile signal types, representing six driving scenarios (i.e., navigation, speed, surrounding vehicles, over the speed limit, headway reductions, and pedestrian status) respectively, and two pattern durations (lower and higher urgencies), on drivers' perception and performance during automated driving. Methods: Sixteen volunteers participated in an experiment utilizing a medium-fidelity driving simulator presenting vibrotactile signals via 20 tactors embedded in the seat back, pan, and …

Prediction Of Length Of Stay In The Emergency Department For Covid-19 Patients: A Machine Learning Approach, Egbe Etu Etu, Leslie Monplaisir, Suzan Arslanturk, Sara Masoud, Celestine Aguwa, Ihor Markevych, Joseph Miller

Faculty Research, Scholarly, and Creative Activity

The coronavirus disease (COVID-19) outbreak has become a global public health threat. The influx of COVID-19 patients has prolonged the length of stay (LOS) in the emergency department (ED) in the United States. Our objective is to develop a reliable prediction model for COVID-19 patient ED LOS and identify clinical factors, such as age and comorbidities, associated with LOS within a '4-hour target.' Data were collected from an urban, demographically diverse hospital in Detroit for all COVID-19 patients' ED presentations from March 16 to December 29, 2020. We trained four machine learning models, namely logistic regression (LR), gradient boosting (GB), …

Stat6 Suppression Prevents Bleomycin-Induced Dermal Fibrosis, Hua Sun, Ashish Damania, Megan L Mair, Eniola Otukoya, Yi-Dong Li, Katherine Polsky, Yuying Zeng, Jeremiah A Alt, Martin J Citardi, David B Corry, Amber U Luong, John Morgan Knight

Faculty, Staff and Student Publications

Unified airway disease, including concurrent asthma and chronic rhinosinusitis (CRS), is a common, but poorly understood disorder with no curative treatment options. To establish a murine model of chronic unified eosinophilic airway inflammation, mice were challenged with Aspergillus niger, and sinonasal mucosa and lung tissue were evaluated by immunohistochemistry, flow cytometry, and gene expression. Inhalation of A niger conidia resulted in a Th2-biased lung and sinus inflammation that typifies allergic asthma and CRS. Gene network and pathway analysis correlated with human disease with upregulation of not only the JAK-STAT and helper T-cell pathways, but also less expected pathways governing …

Clinical Outcome And Gut Development After Insulin-Like Growth Factor-1 Supplementation To Preterm Pigs, Kristine Holgersen, Martin Bo Rasmussen, Galen Carey, Douglas G Burrin, Thomas Thymann, Per Torp Sangild

Faculty, Staff and Students Publications

BACKGROUND: Elevation of circulating insulin-like growth factor-1 (IGF-1) within normal physiological levels may alleviate several morbidities in preterm infants but safety and efficacy remain unclear. We hypothesized that IGF-1 supplementation during the first 1-2 weeks after preterm birth improves clinical outcomes and gut development, using preterm pigs as a model for infants.

METHODS: Preterm pigs were given vehicle or recombinant human IGF-1/binding protein-3 (rhIGF-1, 2.25 mg/kg/d) by subcutaneous injections for 8 days (Experiment 1, n = 34), or by systemic infusion for 4 days (Experiment 2, n = 19), before collection of blood and organs for analyses.

RESULTS: In both …

Research Handling Effects On Stress Hormones, Blood Parameters, And Heart Rate In Juvenile Northern Elephant Seals (Mirounga Angustirostris), Lauren A. Cooley

Master's Theses

Wildlife researchers must balance the need to safely capture and handle their study animals to sample tissues, collect morphological measurements, and attach dataloggers while simultaneously ensuring their results are not confounded by stress artifacts caused by handling. To determine the physiological effects of research activities including chemical immobilization, transport, instrumentation with biologgers, and overnight holding on a model marine mammal species, I collected hormone, blood chemistry, hematology, and heart rate data from 19 juvenile northern elephant seals (Mirounga angustirostris) throughout a translocation experiment. Across my six sampling timepoints, cortisol and aldosterone data revealed a moderate hormonal stress response to handling …

Use Of A Utility-Scale Solar Energy Facility By Avian Populations In Central California, Quratulain Ahmed

Master's Theses

With an ever-increasing demand for renewable energy in response to climate change, utility-scale solar energy (USSE) is on the rise, particularly in California. Although solar energy is viewed as an essential resource for transitioning from a fossil fuel economy, USSE installations can cover thousands of acres of habitat used by avian species. Little is known about the effects of USSE on avian populations, although some evidence suggests that USSE facilities may be leading to bird mortality. The lake-effect hypothesis suggests that birds may mistake solar arrays for large bodies of water resulting in injury or mortality. Though several studies describe …

Pcsk9 Inhibitors In The Management Of Cardiovascular Risk: A Practical Guidance, Xiaoming Jia, Mahmoud Al Rifai, Anum Saeed, Christie M Ballantyne, Salim S Virani

Faculty, Staff and Students Publications

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are potent medications in the toolkit for treatment of atherosclerotic cardiovascular disease. These agents have been well studied in clinical trials supporting their efficacy in dramatically reducing low-density lipoprotein cholesterol (LDL-C) and impact on cardiovascular outcomes. Since the approval of commercial use for PCSK9 inhibitors in 2015, we have also gained significant experience in the use of these therapeutics in the real-world setting. In this article, we review current guideline recommendations, clinical trial evidence on efficacy and safety as well as data on cost-effectiveness, prescription and adherence. We focus primarily on the monoclonal …

Equipping The Saints : Best Practices In Establishing A Five-Fold Equipping Ministry Team, David V. Ford

ATS Dissertations

No abstract provided.

Biblical Preaching, Teaching, And The Charismatic Gifts : Prioritizing The Essentials Of The Great Commission, Sylvester T. Toe

ATS Dissertations

No abstract provided.

A Novel Model Of Gestational Diabetes: Acute High Fat High Sugar Diet Results In Insulin Resistance And Beta Cell Dysfunction During Pregnancy In Mice, Akansha Mishra, Simone Hernandez Ruano, Pradip K Saha, Kathleen A Pennington

Faculty, Staff and Students Publications

Gestational diabetes mellitus (GDM) affects 7–18% of all pregnancies. Despite its high prevalence, there is no widely accepted animal model. To address this, we recently developed a mouse model of GDM. The goal of this work was to further characterize this animal model by assessing insulin resistance and beta cell function. Mice were randomly assigned to either control (CD) or high fat, high sugar (HFHS) diet and mated 1 week later. At day 0 (day of mating) mice were fasted and intraperitoneal insulin tolerance tests (ipITT) were performed. Mice were then euthanized and pancreata were collected for histological analysis. Euglycemic …

Rev-Erb Is Essential In Cardiac Fibroblasts Homeostasis, Xiaokang Luo, Shiyang Song, Lei Qi, Chih-Liang Tien, Hui Li, Weiyi Xu, Theodore Lemuel Mathuram, Thomas Burris, Yuanbiao Zhao, Zheng Sun, Lilei Zhang

Faculty, Staff and Students Publications

REV-ERB agonists have shown antifibrotic effects in the heart and other organs. The function of REV-ERB in the cardiac fibroblasts remains unstudied. Here, we characterize the functional difference of REV-ERB in mouse embryonic fibroblasts and cardiac fibroblasts using genetic deletion of REV-ERBα and ß in vitro. We show that REV-ERB α/β double deleted cardiac fibroblasts have reduced viability and proliferation, but increased migration and myofibroblasts activation. Thus, REV-ERB α/β has essential cell-autonomous role in cardiac fibroblasts in maintaining them in a healthy, quiescent state. We also show that existing REV-ERB agonist SR9009 strongly suppresses cardiac fibroblasts activation but in …

Sr9009 Improves Heart Function After Pressure Overload Independent Of Cardiac Rev-Erb, Hui Li, Shiyang Song, Chih-Liang Tien, Lei Qi, Andrea Graves, Eleni Nasiotis, Thomas P Burris, Yuanbiao Zhao, Zheng Sun, Lilei Zhang

Faculty, Staff and Students Publications

The core clock component REV-ERB is essential for heart function. Previous studies show that REV-ERB agonist SR9009 ameliorates heart remodeling in the pressure overload model with transverse aortic constriction (TAC). However, it is unknown whether SR9009 indeed works through cardiac REV-ERB, given that SR9009 might target other proteins and that REV-ERB in non-cardiac tissues might regulate cardiac functions indirectly. To address this question, we generated the REV-ERBα/β cardiac-specific double knockout mice (cDKO). We found that REV-ERB cardiac deficiency leads to profound dilated cardiac myopathy after TAC compared to wild-type (WT) control mice, confirming the critical role of REV-ERB in protecting …

A Steroid Receptor Coactivator Small Molecule "Stimulator" Attenuates Post-Stroke Ischemic Brain Injury, Lisa K Mcclendon, Roberto L Garcia, Tyler Lazaro, Ariadna Robledo, Viren Vasandani, Zean Aaron Evan Luna, Abhijit S Rao, Aditya Srivatsan, David M Lonard, Clifford C Dacso, Peter Kan, Bert W O'Malley

Faculty, Staff and Students Publications

Introduction: Pathologic remodeling of the brain following ischemic stroke results in neuronal loss, increased inflammation, oxidative stress, astrogliosis, and a progressive decrease in brain function. We recently demonstrated that stimulation of steroid receptor coactivator 3 with the small-molecule stimulator MCB-613 improves cardiac function in a mouse model of myocardial ischemia. Since steroid receptor coactivators are ubiquitously expressed in the brain, we reasoned that an MCB-613 derivative (MCB-10-1), could protect the brain following ischemic injury. To test this, we administered MCB-10-1 to rats following middle cerebral artery occlusion and reperfusion.

Methods: Neurologic impairment and tissue damage responses were evaluated on day …

Steroid Receptor Coactivators – Their Role In Immunity, Yosi Gilad, David M Lonard, Bert W O'Malley

Faculty, Staff and Students Publications

Steroid Receptor Coactivators (SRCs) are essential regulators of transcription with a wide range of impact on human physiology and pathology. In immunology, SRCs play multiple roles; they are involved in the regulation of nuclear factor-κB (NF-κB), macrophage (MΦ) activity, lymphoid cells proliferation, development and function, to name just a few. The three SRC family members, SRC-1, SRC-2 and SRC-3, can exert their immunological function either in an independent manner or act in synergy with each other. In certain biological contexts, one SRC family member can compensate for lack of activity of another member, while in other cases one SRC can …

Foxo1 Is Present In Stomach Epithelium And Determines Gastric Cell Distribution, Wendy M Mckimpson, Taiyi Kuo, Takumi Kitamoto, Sei Higuchi, Jason C Mills, Rebecca A Haeusler, Domenico Accili

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Stomach cells can be converted to insulin-producing cells by Neurog3, MafA, and Pdxl over-expression. Enteroendocrine cells can be similarly made to produce insulin by the deletion of FOXO1. Characteristics and functional properties of FOXO1-expressing stomach cells are not known.

METHODS: Using mice bearing a FOXO1-GFP knock-in allele and primary cell cultures, we examined the identity of FOXO1-expressing stomach cells and analyzed their features through loss-of-function studies with red-to-green fluorescent reporters.

RESULTS: FOXO1 localizes to a subset of Neurog3 and parietal cells. FOXO1 deletion ex vivo or in vivo using Neurog3-cre or Atp4b-cre increased numbers of parietal cells, …

Advancements In The Quest To Map, Monitor, And Manipulate Neural Circuitry, Jessica L Swanson, Pey-Shyuan Chin, Juan M Romero, Snigdha Srivastava, Joshua Ortiz-Guzman, Patrick J Hunt, Benjamin R Arenkiel

Duncan NRI Faculty and Staff Publications

Neural circuits and the cells that comprise them represent the functional units of the brain. Circuits relay and process sensory information, maintain homeostasis, drive behaviors, and facilitate cognitive functions such as learning and memory. Creating a functionally-precise map of the mammalian brain requires anatomically tracing neural circuits, monitoring their activity patterns, and manipulating their activity to infer function. Advancements in cell-type-specific genetic tools allow interrogation of neural circuits with increased precision. This review provides a broad overview of recombination-based and activity-driven genetic targeting approaches, contemporary viral tracing strategies, electrophysiological recording methods, newly developed calcium, and voltage indicators, and neurotransmitter/neuropeptide biosensors …

Quantification Of Behavioral Deficits In Developing Mice With Dystonic Behaviors., Meike E Van Der Heijden, Jason S Gill, Alejandro G Rey Hipolito, Luis E Salazar Leon, Roy V Sillitoe

Duncan NRI Faculty and Staff Publications

Converging evidence from structural imaging studies in patients, the function of dystonia-causing genes, and the comorbidity of neuronal and behavioral defects all suggest that pediatric-onset dystonia is a neurodevelopmental disorder. However, to fully appreciate the contribution of altered development to dystonia, a mechanistic understanding of how networks become dysfunctional is required for early-onset dystonia. One current hurdle is that many dystonia animal models are ideally suited for studying adult phenotypes, as the neurodevelopmental features can be subtle or are complicated by broad developmental deficits. Furthermore, most assays that are used to measure dystonia are not suited for developing postnatal mice. …

Investigation Of Urinary Metabolomics In A Phase I Hookworm Vaccine Trial In Gabon, Madeleine Eunice Betouke Ongwe, Yoanne D Mouwenda, Koen A Stam, Peter G Kremsner, Bertrand Lell, David Diemert, Jeff Bethony, Maria E Bottazzi, Peter J Hotez, Remko V Leeuwen, Martin P Grobusch, Ayola A Adegnika, Oleg A Mayboroda, Maria Yazdanbakhsh

Center for Medical Ethics and Health Policy Staff Publications

Metabolomics provides a powerful tool to study physiological changes in response to various perturbations such as vaccination. We explored whether metabolomic changes could be seen after vaccination in a phase I trial where Gabonese adults living either in rural or semi-urban areas received the subunit hookworm vaccine candidates (Na-GST-1 and Na-APR-1 (M74) adjuvanted with Alhydrogel plus GLA-AF (n = 24) or the hepatitis B vaccine (n = 8) as control. Urine samples were collected and assayed using targeted 1H NMR spectroscopy. At baseline, a set of metabolites significantly distinguished rural from semi-urban individuals. The pre- and post-vaccination comparisons indicated significant …

Evolution Of Genetic Networks For Human Creativity, I Zwir, C Del-Val, M Hintsanen, K M Cloninger, R Romero-Zaliz, A Mesa, J Arnedo, R Salas, G F Poblete, E Raitoharju, O Raitakari, L Keltikangas-Järvinen, G A De Erausquin, I Tattersall, T Lehtimäki, C R Cloninger

Staff and Researcher Publications

The genetic basis for the emergence of creativity in modern humans remains a mystery despite sequencing the genomes of chimpanzees and Neanderthals, our closest hominid relatives. Data-driven methods allowed us to uncover networks of genes distinguishing the three major systems of modern human personality and adaptability: emotional reactivity, self-control, and self-awareness. Now we have identified which of these genes are present in chimpanzees and Neanderthals. We replicated our findings in separate analyses of three high-coverage genomes of Neanderthals. We found that Neanderthals had nearly the same genes for emotional reactivity as chimpanzees, and they were intermediate between modern humans and …

The Surprising Virtues Of Data Loyalty, Woodrow Hartzog, Neil M. Richards

Faculty Scholarship

Lawmakers in the United States and Europe are seriously considering imposing duties of data loyalty that implement ideas from privacy law scholarship, but critics claim such duties are unnecessary, unworkable, overly individualistic, and indeterminately vague. This paper takes those criticisms seriously, and its analysis of them reveals that duties of data loyalty have surprising virtues. Loyalty, it turns out, can support collective well-being by embracing privacy’s relational turn; it can be a powerful state of mind for reenergizing privacy reform; it prioritizes human values rather than potentially empty formalism; and it offers solutions that are flexible and clear rather than …

Trust, Brutality, And Human Dignity: How “Partial Birth Abortion” Helps Shape American Biopolitics, George J. Annas

Faculty Scholarship

In this Article, I explore how nearly continuous public rhetorical challenges to abortion in the political realm first led the public and the courts to turn away from a particular abortion procedure (intact dilation and extraction, also known as partial-birth abortion) which political agitators labeled as “barbaric” and then to view physicians who performed abortions not as legitimate professionals, but simply as “abortionists,” and sometimes as evil “Frankensteins.” “Abortionists” use no “medical judgment” and are unworthy of deference by state legislatures, Congress, or the courts when deciding how or when to perform an abortion. The concentration on the welfare of …

Temporal Stability Of Seagrass Extent, Leaf Area, And Carbon Storage In St. Joseph Bay, Florida: A Semi-Automated Remote Sensing Analysis, Marie Cindy Lebrasse, Blake A. Schaeffer, Megan M. Coffer, Peter J. Whitman, Richard C. Zimmerman, Victoria J. Hill, Kazi A. Islam, Jiang Li, Christopher L. Osburn

OES Faculty Publications

Seagrasses are globally recognized for their contribution to blue carbon sequestration. However, accurate quantification of their carbon storage capacity remains uncertain due, in part, to an incomplete inventory of global seagrass extent and assessment of its temporal variability. Furthermore, seagrasses are undergoing significant decline globally, which highlights the urgent need to develop change detection techniques applicable to both the scale of loss and the spatial complexity of coastal environments. This study applied a deep learning algorithm to a 30-year time series of Landsat 5 through 8 imagery to quantify seagrass extent, leaf area index (LAI), and belowground organic carbon (BGC) …

Imaging Technologies Build Capacity And Accessibility In Phytoplankton Species Identification Expertise For Research And Monitoring: Lessons Learned During The Covid-19 Pandemic, Sophie Clayton, Leah Gibala-Smith, Kathryn Mogatas, Chanel Flores-Vargas, Kayla Marciniak, Maci Wigginton, Margaret R. Mulholland

OES Faculty Publications

As primary producers, phytoplankton play an integral role in global biogeochemical cycles through their production of oxygen and fixation of carbon. They also provide significant ecosystem services, by supporting secondary production and fisheries. Phytoplankton biomass and diversity have been identified by the Global Ocean Observing System (GOOS) as Essential Ocean Variables (EOVs), properties that need to be monitored to better understand and predict the ocean system. Phytoplankton identification and enumeration relies on the skills and expertise of highly trained taxonomic analysts. The training of new taxonomic analysts is intensive and requires months to years of supervised training before an analyst …

Haemosporidians & White-Throated Sparrows (Zonotrichia Albicollis): Parasite Diversity, Factors Influencing Infection, And Effects Of Infection On Fitness, Zoã© Delefortrie

All-Inclusive List of Electronic Theses and Dissertations

Host-parasite interactions play a significant role in the comprehension of co-evolutionary mechanisms such as the host-parasite arms race. Those co-evolutionary mechanisms allow a better understanding of the parasite distribution, emergence of zoonotic diseases, and the impact on hosts populations. In this Ph.D.dissertation, I study the interaction between haemosporidian parasites ( Plasmodium, Haemoproteus , and Leucocytozoon ) and a polymorphic species, the white-throated sparrow ( Zonotrichia albicollis ). First, I examined the occurrence of haemosporidian parasites in a breeding population of white-throated sparrows in the Adirondacks, NY, and assessed their parasite diversity. Then, I evaluated the landscape and individual characteristics influencing …

The Art Of Sim-Making: What To Learn From Film-Making, Fatimah Lateef, Brad Peckler, Eric Saindon, Shruti Chandra, Indrani Sardesai, Mohamed Alwi Abdul Rahman, S Vimal Krishnan, Afrah Abdul Wahid Ali, Rose V Goncalves, Sagar Galwankar

Department of Emergency Medicine Faculty Papers

The components of each stage have similarities as well as differences, which make each unique in its own right. As the film-making and the movie industry may have much we can learn from, some of these will be covered under the different sections of the paper, for example, "Writing Powerful Narratives," depiction of emotional elements, specific industry-driven developments as well as the "cultural considerations" in both. For medical simulation and simulation-based education, the corresponding stages are as follows: DevelopmentPreproductionProductionPostproduction andDistribution. The art of sim-making has many similarities to that of film-making. In fact, there is potentially much to be learnt …