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Expanding the genetic landscape of Rett syndrome to include lysine acetyltransferase 6A(KAT6A)

Journal of Genetics and Genomics 2020年第10期47卷 650-654页

作者： Simranpreet Kaur Nicole J.Van Bergen Bruria Ben-Zeev Emanuela Leonardi Tiong Y.Tan David Coman Benjamin Kamien susan m.white miya St John Dean Phelan Kristin Rigbye Sze Chern Lim michelle C.Torres melanie marty Elena Savva Teresa Zhao Sean massey Alessandra murgia Wendy A.Gold John Christodoulou Brain and mitochondrial Research Group Murdoch Children's Research InstituteMelbourneAustralia Department of Paediatrics University of MelbourneMelbourneAustralia Paediatric Neurology Institute The Edmond and Lily Safra Paediatric HospitalSheba Medical CenterTel HaShomerIsrael Sackler School of medicine Tel Aviv UniversityIsrael molecular Genetics of Neurodevelopment Department of Woman and Child HealthUniversity of PadovaItaly Fondazione Istituto di Ricerca Pediatrica(IRP) Citta della SperanzaPadovaItaly Victorian Clinical Genetics Services Murdoch Children's Research InstituteMelbourneAustralia Department of Paediatrics The Wesley HospitalBrisbaneBrisbaneAustralia Queensland Children's Hospital BrisbaneAustralia School of medicine University of QueenslandBrisbaneAustralia Genetic Services of Western Australia Western AustraliaAustralia Faculty of Health and medical Sciences University of Western AustraliaAustralia Speech and Language Murdoch Children's Research InstituteParkvilleVictoriaAustralia Department of Audiology and Speech Pathology University of MelbourneParkvilleVictoriaAustralia The University of Sydney School of Medical Sciences and Discipline of Child and Adolescent HealthFaculty of Medicine and HealthSydneyAustralia molecular Neurobiology Lab Kids ResearchWestmead Children's HospitalWestmeadSydneyAustralia Kids Neuroscience Centre Kids ResearchChildren's Hospital at WestmeadWestmeadSydneyAustralia

Pathogenic variants in methyl-Cp G protein 2(mECP2;OmIm300005)result in an X-linked,severe,and progressive epigenetic disorder,Rett syndrome(RTT,OmIm:312750),that predominantly affects females(Rett,1966).Using Neul’s revised diagnostic criteria,affected individuals can be clinically classified as classic or atypical RTT(Neul et al.,2010).

关键词： Rett al. landscape

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Adenovirus F40/41 Gastroenteritis-Associated Emphysematous Gastritis:A Case Report

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Infectious Diseases & Immunity 2024年第2期4卷 93-95页

作者： maulik K.Lathiya Abigail T.La Nou maria E.Linnaus susan m.Cullinan Emergency Department Mayo Clinic Health SystemEau Claire 54703WIUSA Critical Care medicine Mayo Clinic Health SystemEau Claire 54703WIUSA General Surgery Department Mayo Clinic Health SystemEau Claire 54703WIUSA

Emphysematous gastritis(EG)is a rare form of gastritis characterized by gastric wall *** is associated with a high mortality *** case report describes a patient with a history of atrial fibrillation treated with apixaban,prior stroke,and schizoaffective disorder who showed epigastric tenderness on ***,no peritonitis signs were recorded,and laboratory values revealed high lactate levels and the presence of adenovirus F40/*** computed tomography scan showed extensive portal venous gas in the left hepatic lobe of the liver,as well as pneumatosis involving the entire stomach,indicating *** diagnosis was histologically confirmed and initially managed medically,which proved inefficacious,necessitating surgical intervention in the form of a laparotomy and esophagojejunostomy with Roux-en-Y *** case report suggests a potential association between EG and adenovirus F40/41–induced gastroenteritis,thereby emphasizing the challenging nature of *** underscores the need for comprehensive research to enhance our understanding of its underlying causes and effective treatment strategies.

关键词： Emphysema Gastritis Human adenovirus F40/41 Immunocompromised

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Erlotinib combination with a mitochondria-targeted ubiquinone effectively suppresses pancreatic cancer cell survival

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World Journal of Gastroenterology 2024年第7期30卷 714-726页

作者： Pui-Yin Leung Wenjing Chen Anissa N Sari Poojitha Sitaram Pui-Kei Wu susan Tsai Jong-In Park Department of Biochemistry Medical College of WisconsinMilwaukeeWI 53226United States Department of Surgery Medical College of WisconsinMilwaukeeWI 53226United States

BACKGROUND Pancreatic cancer is a leading cause of cancer-related *** activity of the epidermal growth factor receptor(EGFR)is often observed in pancreatic cancer,and the small molecule EGFR inhibitor erlotinib has been approved for pancreatic cancer therapy by the food and drug ***,erlotinib alone is ineffective and should be combined with other drugs to improve therapeutic *** previously showed that certain receptor tyrosine kinase inhibitors can increase mitochondrial membrane potential(Δψm),facilitate tumor cell uptake ofΔψm-sensitive agents,disrupt mitochondrial homeostasis,and subsequently trigger tumor cell *** has not been tested for this *** To determine whether erlotinib can elevateΔψm and increase tumor cell uptake ofΔψm-sensitive agents,subsequently triggering tumor cell ***Δψm-sensitive fluorescent dye was used to determine how erlotinib affectsΔψm in pancreatic adenocarcinoma(PDAC)cell *** viability of conventional and patient-derived primary PDAC cell lines in 2D-and 3D cultures was measured after treating cells sequentially with erlotinib and mitochondria-targeted ubiquinone(mitoQ),aΔψm-sensitive *** synergy between erlotinib and mitoQ was then analyzed using SynergyFinder *** preclinical efficacy of the twodrug combination was determined using immune-compromised nude mice bearing PDAC cell line *** Erlotinib elevatedΔψm in PDAC cells,facilitating tumor cell uptake and mitochondrial enrichment ofΔψm-sensitive *** triggered caspase-dependent apoptosis in PDAC cells in culture if used at high doses,while erlotinib pretreatment potentiated low doses of *** suggested that these drugs synergistically induced tumor cell *** with in vitro data,erlotinib and mitoQ combination suppressed human PDAC cell line xenografts in mice more effectively than single treatments of each *** Our findings suggest tha

关键词： Pancreatic cancer Erlotinib mitochondria-targeted ubiquinone mitochondria Combination therapy

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Early anticoagulation in patients with stroke and atrial fibrillation is associated with fewer ischaemic lesions at 1 month: the ATTUNE study

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Stroke & Vascular Neurology 2024年第1期9卷 30-37,I0034页

作者： Angelos Sharobeam Longting Lin Christina Lam Carlos Garcia-Esperon Yash Gawarikar Ronak Patel matthew Lee-Archer Andrew Wong michael Roizman Amanda Gilligan Andrew Lee Kee meng Tan susan Day Christopher Levi Stephen m Davis mark Parsons Bernard Yan melbourne Brain Centre at Royal melbourne Hospital ParkvilleVictoriaAustralia University of New South Wales South Western Sydney Clinical School LiverpoolNew South WalesAustralia Department of Neurology John Hunter HospitalNewcastleNew South WalesAustralia Department of Neurology Calvary Public HospitalCanberraAustralian Capital TerritoryAustralia Department of Neurology Northern Hospital EppingEppingVictoriaAustralia Department of Neurology Royal Brisbane and Women's HospitalHerstonQueenslandAustralia The University of Queensland School of medicine HerstonQueenslandAustralia Neurosciences Clinical Institute Epworth HealthcareRichmondVirginiaAustralia Department of Neurology Austin HealthUniversity of MelbourneHeidelbergVictoriaAustralia Flinders University College of medicine and Public Health AdelaideSouth AustraliaAustralia Department of Neurology Gold Coast University HospitalSouthportQueenslandAustralia The University of Sydney Northern Clinical School St LeonardsNew South WalesAustralia Department of Neurology and Neurophysiology Liverpool HospitalLiverpoolNew South WalesAustralia

Background The optimal time to commence anticoagulation in patients with atrial fibrillation(AF)after ischaemic stroke or transient ischaemic attack(TIA)is unclear,with guidelines differing in recommendations.A limitation of previous studies is the focus on clinically overt stroke,rather than radiologically obvious diffusion-weighted imaging ischaemic *** aimed to quantify silent ischaemic lesions and haemorrhages on mRI at 1month in patients commenced on early(mic lesions and more haemorrhages in the early anticoagulant group at 1-month *** A prospective multicentre,observational cohort study was performed at 11 Australian stroke *** and mRI data were collected at baseline and follow-up,with blinded imaging assessment performed by two *** of commencement of anticoagulation was at the discretion of the treating stroke *** We recruited 276 patients of whom 208 met the eligibility *** average age was 74.2 years(SD±10.63),and 79(38%)patients were *** National Institute of Health Stroke Scale score was 5(IQR 1–12).median baseline ischaemic lesion volume was 5mL(IQR 2–17).There were a greater number of new ischaemic lesions on follow-up mRI in patients commenced on anticoagulation≥4days after index event(17%vs 8%,p=0.04),but no difference in haemorrhage rates(22%vs 32%,p=0.10).Baseline ischaemic lesion volume of≤5mL was less likely to have a new haemorrhage at 1month(p=0.02).There was no difference in haemorrhage rates in patients with an initial ischaemic lesion volume of>5mL,regardless of anticoagulation *** Commencing anticoagulationmic lesions at 1month in AF *** is no increased rate of haemorrhage with early *** results suggest that early anticoagulation after mild-to-moderate acute ischaemic stroke associated w

关键词： patients lesions ischaemic

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Risk factors for musculoskeletal injuries in the military: a qualitative systematic review of the literature from the past two decades and a new prioritizing injury model

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military medical Research 2022年第4期9卷 444-483页

作者： Stefan Sammito Vedran Hadzic Thomas Karakolis Karen R.Kelly susan P.Proctor Ainars Stepens Graham.white Wes O.Zimmermann Section Experimental Aerospace medicine Research German Air Force Centre of Aerospace MedicineFlughafenstraBe 151147 CologneGermany Occupational medicine Faculty of MedicineOtto-Von-Guericke-University of Magdeburg39120 MagdeburgGermany Faculty of Sport University of Ljubljana1000 LjubljanaSlovenia Defence Research and Development Canada TorontoON M3K 2C9Canada Warfighter Performance Naval Health Research CenterSan DiegoCA 921063599USA military Performance Division US Army Research Institute of Environmental MedicineNatickMA 01760USA Research Service VA Boston Healthcare SystemBostonMA 02130USA Centre for military medicine Research Riga Stradins UniversityRiga 1007Latvia Human and Social Sciences Group Defense Science and Technology LaboratoryPortsdown Hill RoadFareham PO176ADUK Department of military Sports medicine Royal Netherlands Army3584 AB UtrechtThe Netherlands Department of military/Emergency medicine Uniformed Services University of the Health SciencesBethesdaMD 20814USA.

Background: musculoskeletal injuries(mSkIs) are a leading cause of health care utilization, as well as limited duty and disability in the US military and other armed forces. mSkIs affect members of the military during initial training,operational training, and deployment and have a direct negative impact on overall troop readiness. Currently, a systematic overview of all risk factors for mSkIs in the military is not ***: A systematic literature search was carried out using the Pubmed, Ovid/medline, and Web of Science databases from January 1, 2000 to September 10, 2019. Additionally, a reference list scan was performed(using the “snowball method”). Thereafter, an international, multidisciplinary expert panel scored the level of evidence per risk factor, and a classification of modifiable/non-modifiable was ***: In total, 176 original papers and 3 meta-analyses were included in the review. A list of 57 reported potential risk factors was formed. For 21 risk factors, the level of evidence was considered moderate or strong. Based on this literature review and an in-depth analysis, the expert panel developed a model to display the most relevant risk factors identified, introducing the idea of the “order of importance” and including concepts that are modifiable/nonmodifiable, as well as extrinsic/intrinsic risk ***: This is the qualitative systematic review of studies on risk factors for mSkIs in the military that has attempted to be all-inclusive. A total of 57 different potential risk factors were identified, and a new, prioritizing injury model was developed. This model may help us to understand risk factors that can be addressed, and in which order they should be prioritized when planning intervention strategies within military groups.

关键词： military musculoskeletal injuries Risk factors Prevention Intervention Injury

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How well does XAD resin extraction recover halogenated disinfection byproducts for comprehensive identification and toxicity testing?

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Journal of Environmental Sciences 2022年第7期34卷 264-275页

作者： Xiaobin Liao Joshua m.Allen Caroline O.Granger susan D.Richardson Department of Chemistry and Biochemistry University of South CarolinaColumbiaSouth Carolina 29208USA Institute of municipal and Environmental Engineering College of Civil EngineeringHuaqiao UniversityFujian 361021China Currently at LanzaTech 535 Commerce DriveSopertonGeorgia 30457USA

Halogenated disinfection byproducts(DBPs) are an unintended consequence of drinking water disinfection, and can have significant toxicity. XAD resins are commonly used to extract and enrich trace levels of DBPs for comprehensive, nontarget identification of DBPs and also for in vitro toxicity studies. However, XAD resin recoveries for complete classes of halogenated DBPs have not been evaluated, particularly for low, environmentally relevant levels(ng/L to low μg/L). Thus, it is not known whether levels of DBPs or the toxicity of drinking water might be underestimated. In this study, DAX-8/XAD-2 layered resins were evaluated, considering both adsorption and elution from the resins, for extracting 66 DBPs from water. Results demonstrate that among the 7 classes of DBPs investigated, trihalomethanes(THms), including iodo-THms, were the most efficiently adsorbed, with recovery of most THms ranging from 50%-96%, followed by halonitromethanes(40%-90%). The adsorption ability of XAD resins for haloacetonitriles, haloacetamides, and haloacetaldehydes was highly dependent on the individual species. The adsorption capacity of XAD resins for haloacetic acids was lower(5%-48%), even after adjusting to p H 1 before extraction. Recovery efficiency for most DBPs was comparable with their adsorption, as most were eluted effectively from XAD resins by ethyl acetate. DBP polarity and molecular weight were the two most important factors that determine their recovery. Recovery of trichloromethane, iodoacetic acid, chloro-and iodo-acetonitrile, and chloroacetamide were among the lowest, which could lead to underestimation of toxicity, particularly for iodoacetic acid and iodo-acetonitrile, which are highly toxic.

关键词： XAD resins Disinfection byproducts DBPs Recovery Toxicity

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Local tips, global impact: community-driven measures as avenues of promoting inclusion in the control of neglected tropical diseases: a case study in Kenya

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Infectious Diseases of Poverty 2022年第4期11卷 81-90页

作者： Elizabeth A.Ochola Diana m.S.Karanja susan J.Elliott Department of Geography and Environmental management University ofWaterlooWaterlooONCanada

Background:Neglected tropical diseases(NTDs)affect poor populations with little or no’’political voice’to influence control *** most NTDs have interventions that work,the biggest challenge remains in delivering targeted interventions to affected populations residing in areas experiencing weak health *** the upward development trends in most countries of sub-Saharan Africa(SSA),the healthcare worker to population ratio remains exceptionally low,with some areas not served at all;thus,there is a need to involve other personnel for school and community-based healthcare ***,the current community-based programs suffer from inconsistent community participation due to a lack of coordinated response,and an expanded intervention agenda that lacks context-specific solutions applicable to rural,urban,and marginalized ***:This research investigated the capacity of local communities to address the burden of *** by the social theory of human capability,the research collected primary qualitative data by conducting key informant interviews and focus group discussions of people infected or affected by *** interview data were collected and transcribed verbatim for thematic analysis using Nvivo version ***:Our findings reveal,first,a need for intersectoral collaboration between governments and affected populations for inclusive and sustainable NTD ***,a’’bottom-up’approach that enhances capacity building,sensitization,and behaviour change for improved uptake of NTD ***,the enforcement of Public Health Legislative Acts that mandates the reporting and treatment of NTDs such as ***,the establishment of support groups and counseling services to assist persons suffering from debilitating and permanent effects of ***:Our research demonstrates the importance of human agency in encouraging new forms of participation leading to the co-production of inclusive and susta

关键词： Neglected tropical diseases Control Community-driven measure Local solution Global impact Inclusion Kenya

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Genome and clonal hematopoiesis stability contrasts with immune,cfDNA,mitochondrial,and telomere length changes during short duration spaceflight

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Precision Clinical medicine 2024年第1期7卷 1-13页

作者： J.Sebastian Garcia-medina Karolina Sienkiewicz S.Anand Narayanan Eliah G.Overbey Kirill Grigorev Krista A.Ryon marissa Burke Jacqueline Proszynski Braden Tierney Caleb m.Schmidt Nuria mencia-Trinchant Remi Klotz Veronica Ortiz Jonathan Foox Christopher Chin Deena Najjar Irina matei Irenaeus Chan Carlos Cruchaga Ashley Kleinman JangKeun Kim Alexander Lucaci Conor Loy Omary mzava Iwijn De Vlaminck Anvita Singaraju Lynn E.Taylor Julian C.Schmidt michael A.Schmidt Kelly Blease Juan moreno Andrew Boddicker Junhua Zhao Bryan Lajoie Andrew Altomare Semyon Kruglyak Shawn Levy min Yu Duane C.Hassane susan m.Bailey Kelly Bolton Jaime mateus Christopher E.mason Department of Physiology and Biophysics Weill Cornell MedicineCornell UniversityNew YorkNY 10021USA The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine Weill Cornell MedicineNew YorkNY 10021USA Department of Immunology Weill Cornell MedicineCornell UniversityNew YorkNY 10021USA Department of Stem Cell Biology and Regenerative medicine Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCA 90033USA Space Exploration Technologies Corporation HawthomeCA 90250USA Sovaris Aerospace BoulderCO 80302USA Advanced Pattern Analysis&Human Performance Group BoulderCO 80302USA Children's Cancer and Blood Foundation Laboratories Departments of Pediatrics and Cell and Developmental BiologyDrukier Institute for Children's HealthMeyer Cancer CenterWeill Cornell MedicineNew YorkNY 10021USA meyer Cancer Center Weill Cornell MedicineNew YorkNY 10065USA Department of Nutrition and Integrative Physiology Florida State UniversityTallahasseeFL 32306USA Department of Systems Engineering Colorado State UniversityFort CollinsCO 80523USA Element Biosciences San DiegoCA 10055USA Department of Environmental and Radiological Health Sciences Colorado State UniversityFort CollinsCO 80523USA Cell and molecular Biology Program Colorado State UniversityFort CollinsCO 80523USA BioAstra Inc New YorkNYUSA Washington University St Louis Oncology Division St.LouisMO 63100USA meinig School of Biomedical Engineering Cornell UniversityIthacaNY 14853USA The Feil Family Brain and mind Research Institute Weill Cornell MedicineNY 10021USA WorldQuant Initiative for Quantitative Prediction Weill Cornell MedicineNew YorkNY 10021USA

Background The Inspiration4(I4)mission,the first all-civilian orbital flight mission,investigated the physiological effects of short-duration spaceflight through a multi-omic *** advances,there remains much to learn about human adaptation to spaceflight's unique challenges,including microgravity,immune system perturbations,and radiation *** To provide a detailed genetics analysis of the mission,we collected dried blood spots pre-,during,and post-flight for DNA *** length was measured by quantitative PCR,while whole genome and cfDNA sequencing provided insight into genomic stability and immune adaptations.A robust bioinformatic pipeline was used for data analysis,including variant calling to assess mutational *** Telomere elongation occurred during spaceflight and shortened after return to ***-free DNA analysis revealed increased immune cell signatures *** significant clonal hematopoiesis of indeterminate potential(CHIP)or whole-genome instability was *** long-term gene expression changes across immune cells suggested cellular adaptations to the space environment persisting months *** Our findings provide valuable insights into the physiological consequences of short-duration spaceflight,with telomere dynamics and immune cell gene expression adapting to spaceflight and persisting after return to *** sequencing data will serve as a reference point for studying the early development of CHIP in astronauts,an understudied phenomenon as previous studies have focused on career *** study will serve as a reference point for future commercial and non-commercial spaceflight,low Earth orbit(LEO)missions,and deep-space exploration.

关键词： genomes clonal hematopoiesis stability immune mitochondria ribosomes spaceflight

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Growth differentiation factor 5:a neurotrophic factor with neuroprotective potential in Parkinson’s disease

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Neural Regeneration Research 2022年第1期17卷 38-44页

作者： susan R.Goulding Jayanth Anantha Louise m.Collins Aideen m.Sullivan Gerard W.O’Keeffe Department of Anatomy and Neuroscience and Cork Neuroscience CentreUniversity College CorkCorkIreland Department of Physiology University College CorkCorkIreland

Parkinson’s disease is the most common movement disorder worldwide,affecting over 6 million *** is an age-related disease,occurring in 1%of people over the age of 60,and 3%of the population over 80 *** disease is characterized by the progressive loss of midbrain dopaminergic neurons from the substantia nigra,and their axons,which innervate the striatum,resulting in the characteristic motor and non-motor symptoms of Parkinson’s *** is paralleled by the intracellular accumulation ofα-synuclein in several regions of the nervous *** therapies are solely symptomatic and do not stop or slow disease *** promising disease-modifying strategy to arrest the loss of dopaminergic neurons is the targeted delivery of neurotrophic factors to the substantia nigra or striatum,to protect the remaining dopaminergic neurons of the nigrostriatal ***,clinical trials of two well-established neurotrophic factors,glial cell line-derived neurotrophic factor and neurturin,have failed to meet their primary *** failure is thought to be at least partly due to the downregulation byα-synuclein of Ret,the common co-receptor of glial cell line-derived neurorophic factor and ***/differentiation factor 5 is a member of the bone morphogenetic protein family of neurotrophic factors,that signals through the Ret-independent canonical Smad signaling ***,we review the evidence for the neurotrophic potential of growth/differentiation factor 5 in in vitro and in vivo models of Parkinson’s *** discuss new work on growth/differentiation factor 5’s mechanisms of action,as well as data showing that viral delivery of growth/differentiation factor 5 to the substantia nigra is neuroprotective in theα-synuclein rat model of Parkinson’s *** data highlight the potential for growth/differentiation factor 5 as a disease-modifying therapy for Parkinson’s disease.

关键词： adeno-associated virus bone morphogenetic protein dopaminergic neurons growth/differentiation factor 5 neurodegeneration neuroprotection neurotrophic factor Parkinson’s disease Smad signaling α-synuclein

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The role of emergency incident type in identifying first responders' health exposure risks

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Journal of Safety Science and Resilience 2023年第2期4卷 167-173页

作者： Emily J.Haas Katherine N.Yoon Alexa Furek megan Casey susan m.moore National Personal Protective Technology Laboratory(NPPTL) National Institute for Ocupational Safety and Health(NIOSH)PittsburghPA 15236United States National Personal Protective Technology Laboratory(NPPTL) National Institute forOccupational Safety and Health(NIOSH)MorgantownWV2605United States

Fire-based emergency management service(EmS)personnel are dispatched to various incidents daily,many of which have unique occupational *** fully understand the variability of incident types and how to best pre-pare and respond,an exploration of the *** system of incident types is *** study uses potential exposure to SARS-CoV-2 as a case example to understand if and how coding categories for incident call types may be updated to improve data standardization and emergency response decision *** received emergency response incident data generated by three fire department computer-aided dispatch(CAD)systems between march and September *** incident was labeled EmS,Fire,or *** the 162,766 incidents,approximately 8.1%(n=13,144)noted potential SARS-CoV-2 exposure within their narrative descriptions of which 86.3%were coded as EmS,9.9%as Fire,and 3.9%as *** assess coding variability across incident types,researchers used the original 3-incident type variable and a new 5-incident type variable reassigned by researchers into EmS,Fire,Other,Hazmat,and motor *** regressions compared differences in potential exposure using the 3-and 5-incident type *** evaluating the 3-incident type variable,those respond-ing to a Fire versus an EmS incident were 84%less likely to be associated with potential exposure to *** the 5-incident type variable,those responding to Fire incidents were 77%less likely to be associated with a potential exposure than those responding to EmS *** in potential exposure between the 3-and 5-incident type models show the need to understand how incident types are *** demonstrates the need for data standardization to accurately categorize incident types to improve emergency preparedness and *** have implications for incident type coding at fire department municipality and national levels.

关键词： Emergencymedical se Firefighter Incident type Surveillance Telecommunicator

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