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BACKGROUND: Spatial epidemiology has emerged as an important subfield of epidemiology over the past quarter century. We trace the origins of spatial epidemiology and note that its emergence coincided with technological developments in spatial statistics and geography. We hypothesize that spatial epidemiology makes important contributions to descriptive epidemiology and analytic risk-factor studies but is not yet aligned with epidemiology's current focus on causal inference and intervention. METHODS: We conducted a systematic review of studies indexed in PubMed that used the term "spatial epidemiolog*" in the title, abstract, or keywords. Excluded articles were not written in English, examined disease in animals, or reported biologic pathogen distribution only. We coded the included papers into five categories (review, demonstration of method, descriptive, analytic, and intervention) and recorded the unit of analysis (i.e., individual vs. ecological). We additionally examined articles coded as analytic ecologic studies using scales for lexical content. RESULTS: A total of 482 articles met the inclusion criteria, including 76 reviews, 117 demonstrations of methods, 122 descriptive studies, 167 analytic studies, and 0 intervention studies. Demonstration studies were most common from 2006 to 2014, and analytic studies were most common after 2015. Among the analytic ecologic studies, those published in later years used more terms relevant to spatial statistics (incidence rate ratio =1.3; 95% confidence interval [CI] = 1.1, 1.5) and causal inference (incidence rate ratio =1.1; 95% CI = 1.1, 1.2). CONCLUSIONS: Spatial epidemiology is an important and growing subfield of epidemiology. We suggest a re-orientation to help align its practice with the goals of contemporary epidemiology.
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Análise Espacial , Humanos , Métodos Epidemiológicos , EpidemiologiaRESUMO
INTRODUCTION: This study examined the effectiveness of three physical environmental roadway interventions (enhanced crossings, speed humps, and turn traffic calming) in preventing crashes involving pedestrian and cyclist injury and mortality in New York City. METHODS: We examined crashes that occurred within a 100-foot radius of intervention and control sites from 2015 to 2019. We used a staggered difference-in-difference design to estimate the association between each intervention type and pedestrian and cyclist crash outcomes. RESULTS: Estimates for enhanced crossings and speed humps included the possibility of no association with crashes, but estimates for turn traffic calming interventions showed reduced odds of crashes involving pedestrian injury by 16% (OR 0.84, 95% CI 0.74 to 0.95) and crashes involving pedestrian fatality by 80% (OR 0.20, 95% CI 0.08 to 0.47). When stratifying by street segment length as a proxy for areas with high speeding risk, turn traffic calming treatments appeared to be most effective at intersections connected to long street segments. DISCUSSION: Turn traffic calming may substantially reduce crash risks for pedestrians. Municipalities can prioritise this physical environmental intervention, especially at turns near long street segments, as a low-cost intervention with substantial public health impact.
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INTRODUCTION: Firearm violence is a major public health issue in the USA. There is growing evidence that firearm violence is associated with higher ambient temperatures. The aim of this study was to test competing hypotheses that could explain associations between temperature and firearm violence: temperature-aggression theory and routine activities theory. METHODS: We examined associations between elevated daily temperatures and shooting incidents in four US cities: Chicago, Illinois; Cincinnati, Ohio; New York, New York and Philadelphia, Pennsylvania. Temperature was operationalised using two different measures: daily maximum temperature and deviations of the daily maximum temperature from 30-year averages. Generalised linear autoregressive moving average models related temperature to shooting incidence while controlling for seasonal effects. RESULTS: As maximum daily temperature deviates from the expected, there was an association with increased shooting incidents in all four cities (eg, New York: b=0.014, 95% CI=0.011 to 0.017). An interaction term created by multiplying daily maximum temperature by the daily difference of maximum temperature from a 30-year average was also found to have a positive association in all four cities (eg, New York: b=0.020, 95% CI=0.016 to 0.025). DISCUSSION: These findings accord with previous studies demonstrating a positive relationship between temperature and firearm violence and further support temperature-aggression theory as the primary causal mechanism.
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BACKGROUND: Firearm violence is an intensifying public health problem in the United States. News reports shape the way the public and policy makers understand and respond to health threats, including firearm violence. To better understand how firearm violence is communicated to the public, we aimed to determine the extent to which firearm violence is framed as a public health problem on television news and to measure harmful news content as identified by firearm-injured people. METHODS: This is a quantitative content analysis of Philadelphia local television news stories about firearm violence using a database of 7,497 clips. We compiled a stratified sample of clips aired on two randomly selected days/month from January-June 2021 from the database (n = 192 clips). We created a codebook to measure public health frame elements and to assign a harmful content score for each story and then coded the clips. Characteristics of stories containing episodic frames that focus on single shooting events were compared to clips with thematic frames that include broader social context for violence. RESULTS: Most clips employed episodic frames (79.2%), presented law enforcement officials as primary narrators (50.5%), and included police imagery (79.2%). A total of 433 firearm-injured people were mentioned, with a mean of 2.8 individuals shot included in each story. Most of the firearm-injured people featured in the clips (67.4%) had no personal information presented apart from age and/or gender. The majority of clips (84.4%) contained at least one harmful content element. The mean harmful content score/clip was 2.6. Public health frame elements, including epidemiologic context, root causes, public health narrators and visuals, and solutions were missing from most clips. Thematic stories contained significantly more public health frame elements and less harmful content compared to episodic stories. CONCLUSIONS: Local television news produces limited public health coverage of firearm violence, and harmful content is common. This reporting likely compounds trauma experienced by firearm-injured people and could impede support for effective public health responses to firearm violence. Journalists should work to minimize harmful news content and adopt a public health approach to reporting on firearm violence.
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Armas de Fogo , Saúde Pública , Televisão , Violência , Humanos , Philadelphia , Televisão/estatística & dados numéricos , Armas de Fogo/estatística & dados numéricos , Violência/estatística & dados numéricos , Violência/prevenção & controle , Ferimentos por Arma de Fogo/prevenção & controle , Ferimentos por Arma de Fogo/epidemiologia , Violência com Arma de Fogo/prevenção & controle , Violência com Arma de Fogo/estatística & dados numéricosRESUMO
BACKGROUND: Australian children and adolescents were among the last local cohorts offered COVID-19 vaccines. Despite promising initial uptake, coverage subsequently plateaued, requiring further efforts to improve access and build parents' recognition of the importance of COVID-19 vaccination. We sought to understand West Australian (WA) parents' willingness to vaccinate their children to inform strategies for improving uptake at the time in which they were becoming eligible. METHODS: We undertook in-depth qualitative interviews with 30 parents of children aged 5-17 years from June - December 2021. During this period, children aged 12-15 years became eligible for vaccination; children aged 5-11 years became eligible shortly thereafter. Data were thematically analysed in NVivo. RESULTS: Most parents intended on vaccinating their children once eligible. Parents sought to protect their children, to protect the community, to resume travel, and to get back to "normal". They reflected that vaccination against key infectious threats is a routine activity in childhood. Some were concerned about the vaccine, particularly mRNA vaccines, being new technology or impacting fertility. "Wait-awhiles" wanted to see what other parents would do or were delaying until they felt that there was a higher risk of COVID-19 in WA. Most parents of younger children wanted their child to be vaccinated at the general practice clinic due to familiarity and convenience. Parents were particularly eager for clear and consistent messaging about vaccination of children and adolescents, including safety, importance, scientific evidence, and personal stories. CONCLUSION: For future pandemic vaccinations pertaining to children, governments and health officials need to address parents' concerns and meet their preferences for the delivery of the vaccine program to children and adolescents.
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COVID-19 , Adolescente , Criança , Humanos , COVID-19/prevenção & controle , Vacinas contra COVID-19/uso terapêutico , Austrália/epidemiologia , Pesquisa Qualitativa , PaisRESUMO
Incompatibility group C (IncC) plasmids are large (50-400 kb), broad host range plasmids that drive the spread of genes conferring resistance to all classes of antibiotics, most notably the blaNDM gene that confers resistance to last-line carbapenems and the mcr-3 gene that confers resistance to colistin. Several recent studies have improved our understanding of the basic biological mechanisms driving the success of IncC, in particular the identification of multiple novel IncC conjugation genes by transposon directed insertion-site sequencing. Here, one of these genes, dtrJ, was examined in further detail. The dtrJ gene is located in the DNA transfer locus on the IncC backbone, and quantitative reverse-transcriptase PCR analysis revealed it is transcribed in the same operon as the DNA transfer genes traI and traD (encoding the relaxase and coupling protein, respectively) and activated by the AcaDC regulatory complex. We confirmed that DtrJ is not required for pilus biogenesis or mate pair formation. Instead, DtrJ localizes to the membrane, where it interacts with the coupling protein TraD and functions as an IncC DNA transfer protein. Overall, this work has defined the role of DtrJ in DNA transfer of IncC plasmids during conjugation.
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Conjugação Genética/genética , Elementos de DNA Transponíveis/genética , Farmacorresistência Bacteriana Múltipla/genética , Escherichia coli/genética , Plasmídeos/genética , Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Colistina/farmacologia , Escherichia coli/efeitos dos fármacos , Proteínas de Escherichia coli/genética , Transferases (Outros Grupos de Fosfato Substituídos)/genética , beta-Lactamases/genéticaRESUMO
STUDY QUESTION: Are transcriptomic profiles altered in ovarian granulosa cells (GCs) and peripheral blood mononuclear cells (PBMNCs) of women with polycystic ovary syndrome (PCOS) compared to young poor responders (YPR) and women with normal response to ovarian stimulation? SUMMARY ANSWER: RNA expression profiles in ovarian GCs and PBMNCs were significantly altered in patients with PCOS compared with normoresponder controls (CONT) and YPR. WHAT IS KNOWN ALREADY: PCOS is characterised by a higher number of follicles at all developmental stages. During controlled ovarian hyperstimulation, PCOS women develop a larger number of follicles as a result of an exacerbated response, with an increased risk of ovarian hyperstimulation syndrome. Despite the number of developing follicles, they are often heterogeneous in both size and maturation stage, with compromised quality and retrieval of immature oocytes. Women with PCOS appear to have a longer reproductive lifespan, with a slightly higher menopausal age than the general population, in addition to having a higher antral follicular count. As a result, the ovarian follicular dynamics appear to differ significantly from those observed in women with poor ovarian response (POR) or diminished ovarian reserve. STUDY DESIGN, SIZE, DURATION: Transcriptomic profiling with RNA-sequencing and validation using quantitative reverse transcription PCR (qRT-PCR). Women with PCOS (N = 20), YPR (N = 20) and CONT (N = 20). Five patients for each group were used for sequencing and 15 samples per group were used for validation. PARTICIPANTS/MATERIALS, SETTING, METHODS: PCOS was defined using the revised Rotterdam diagnostic criteria for PCOS. The YPR group included women <35 years old with <4 mature follicles (at least 15 mm) on the day of the trigger. According to internal data, this group represented the bottom 15th percentile of patients' responses in this age group. It was consistent with Patient-Oriented Strategies Encompassing Individualize D Oocyte Number (POSEIDON) criteria for POR (Group 3). The young CONT group included women <35 years without PCOS or anovulation, who developed >14 mature follicles (at least 15 mm on transvaginal ultrasound). According to internal data, a threshold of >14 mature follicles was established to represent the top 25% of patients in this age group in this clinic.Overall, n = 60 GCs and PBMNCs samples were collected and processed for total RNA extraction. To define the transcriptomic cargo of GCs and PBMNCs, RNA-seq libraries were successfully prepared from samples and analysed by RNA-seq analysis. Differential gene expression analysis was used to compare RNA-seq results between different groups of samples. Ingenuity pathway analysis was used to perform Gene Ontology and pathways analyses. MAIN RESULTS AND THE ROLE OF CHANCE: In PBMNCs of PCOS, there were 65 differentially expressed genes (DEGs) compared to CONT, and 16 compared to YPR. In GCs of PCOS, 4 genes showed decreased expression compared to CONT, while 58 genes were differentially expressed compared to YPR. qRT-PCR analysis confirmed the findings of the RNA-seq. The functional enrichment analysis performed revealed that DEGs in GCs of PCOS compared to CONT and YPR were prevalently involved in protein ubiquitination, oxidative phosphorylation, mitochondrial dysfunction and sirtuin signaling pathways. LARGE SCALE DATA: The data used in this study is partially available at Gene Ontology database. LIMITATIONS, REASONS FOR CAUTION: The analysis in PBMNCs could be uninformative due to inter-individual variability among patients in the same study groups. Despite the fact that we considered this was the best approach for our study's novel, exploratory nature. WIDER IMPLICATIONS OF THE FINDINGS: RNA expression profiles in ovarian GCs and PBMNCs were altered in patients with PCOS compared with CONT and YPR. GCs of PCOS patients showed altered expression of several genes involved in oxidative phosphorylation, mitochondrial function and sirtuin signaling pathways. This is the first study to show that the transcriptomic landscape in GCs is altered in PCOS compared to CONT and YPR. STUDY FUNDING/COMPETING INTEREST(S): This study was partially supported by grant PI18/00322 from Instituto de Salud Carlos III, and European Regional Development Fund (FEDER), 'A way to make Europe' awarded to S.H. M.C., S.H., S.T., L.R., M.R., I.R., A.P. and R.C. declare no conflict of interests concerning this research. E.S. is a consultant for and receives research funding from the Foundation for Embryonic Competence. TRIAL REGISTRATION NUMBER: N/A.
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Síndrome do Ovário Policístico , Sirtuínas , Feminino , Células da Granulosa , Humanos , Leucócitos Mononucleares , Síndrome do Ovário Policístico/genética , RNA , TranscriptomaRESUMO
BACKGROUND: Oxford Nanopore Technology (ONT) long-read sequencing has become a popular platform for microbial researchers due to the accessibility and affordability of its devices. However, easy and automated construction of high-quality bacterial genomes using nanopore reads remains challenging. Here we aimed to create a reproducible end-to-end bacterial genome assembly pipeline using ONT in combination with Illumina sequencing. RESULTS: We evaluated the performance of several popular tools used during genome reconstruction, including base-calling, filtering, assembly, and polishing. We also assessed overall genome accuracy using ONT both natively and with Illumina. All steps were validated using the high-quality complete reference genome for the Escherichia coli sequence type (ST)131 strain EC958. Software chosen at each stage were incorporated into our final pipeline, MicroPIPE. Further validation of MicroPIPE was carried out using 11 additional ST131 E. coli isolates, which demonstrated that complete circularised chromosomes and plasmids could be achieved without manual intervention. Twelve publicly available Gram-negative and Gram-positive bacterial genomes (with available raw ONT data and matched complete genomes) were also assembled using MicroPIPE. We found that revised basecalling and updated assembly of the majority of these genomes resulted in improved accuracy compared to the current publicly available complete genomes. CONCLUSIONS: MicroPIPE is built in modules using Singularity container images and the bioinformatics workflow manager Nextflow, allowing changes and adjustments to be made in response to future tool development. Overall, MicroPIPE provides an easy-access, end-to-end solution for attaining high-quality bacterial genomes. MicroPIPE is available at https://github.com/BeatsonLab-MicrobialGenomics/micropipe .
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Escherichia coli , Genoma Bacteriano , Biologia Computacional , Sequenciamento de Nucleotídeos em Larga Escala , Análise de Sequência de DNA , Fluxo de TrabalhoRESUMO
People who identify as lesbian, gay, bisexual, and/or transgender (LGBT) experience disparate levels of psychological distress due to marginalization, yet there are also opportunities for community connectedness and sociopolitical involvement in identify-specific issues and organizations, which may improve psychological well-being. This study contributes to intersectional research on LGBT psychological well-being by locating LGBT community connectedness as a mediator of the associations between well-being and (a) LGBT sociopolitical involvement and (b) being out as LGBT among a sample of predominately LGBT-identified adults in the United States and Puerto Rico (n = 4940) across four racial/ethnic identity groups: non-Hispanic Black, Latinx/Hispanic, non-Hispanic White, and other races/ethnicities. Analyses revealed that separate models were operating across racial/ethnic identity groups. Path analysis further showed that LGBT community connectedness mediated (either partially or fully) the effects of both LGBT sociopolitical involvement and outness on well-being. Direct effects on well-being were also found for family support across all groups and for outness only among the non-Hispanic White and other races/ethnicities groups. Community leaders and practitioners should seek to create opportunities for LGBT sociopolitical involvement and other activities that may facilitate feeling connected to LGBT community as part of efforts to promote LGBT well-being.
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Homossexualidade Feminina , Minorias Sexuais e de Gênero , Pessoas Transgênero , Adulto , Etnicidade , Feminino , Hispânico ou Latino , Humanos , Estados UnidosRESUMO
The importance of phonological awareness (PA) for the acquisition of literacy skills has been widely recognized. Across languages, PA is commonly examined using the Oddity test, however, for Chinese-speaking children, Pinyin invented spelling is recommended as being a more powerful tool to assess PA. However, it is still unclear whether this holds true for learners of Chinese as a second language (CSL). To address this issue, we administered an oddity test and a Pinyin invented spelling task to explore Chinese PA in 43 Arabic and 40 English CSL learners at pre-intermediate and intermediate levels. The results generated two major findings. First, Pinyin invented spelling revealed more significant cross-group differences in Chinese PA between the Arabic and English CSL learners than the oddity test. Second, the participants' performance in Pinyin invented spelling was a stronger predictor of character-reading and character-writing skills than their performance in the oddity test. The overall findings suggest that Pinyin invented spelling may be a more powerful measurement of Chinese PA for CSL learners in comparison to the conventional test, in line with the findings reported for Chinese-speaking children. The theoretical implications for understanding the role of phonological skills in the growth of Chinese literacy skills and practical suggestions for measuring Chinese PA are proposed.
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Idioma , Fonética , Conscientização , Criança , China , Humanos , LeituraRESUMO
Klebsiella species are problematic pathogens in neonatal units and may cause outbreaks, for which the sources of transmission may be challenging to elucidate. We describe the use of whole-genome sequencing (WGS) to investigate environmental sources of transmission during an outbreak of extended-spectrum-ß-lactamase (ESBL)-producing Klebsiella michiganensis colonizing neonates. Ceftriaxone-resistant Klebsiella spp. isolated from neonates (or their mothers) and the hospital environment were included. Short-read sequencing (Illumina) and long-read sequencing (MinION; Oxford Nanopore Technologies) were used to confirm species taxonomy, to identify antimicrobial resistance genes, and to determine phylogenetic relationships using single-nucleotide polymorphism profiling. A total of 21 organisms (10 patient-derived isolates and 11 environmental isolates) were sequenced. Standard laboratory methods identified the outbreak strain as an ESBL-producing Klebsiella oxytoca, but taxonomic assignment from WGS data suggested closer identity to Klebsiella michiganensis Strains isolated from multiple detergent-dispensing bottles were either identical or closely related by single-nucleotide polymorphism comparison. Detergent bottles contaminated by K. michiganensis had been used for washing milk expression equipment. No new cases were identified once the detergent bottles were removed. Environmental reservoirs may be an important source in outbreaks of multidrug-resistant organisms. WGS, in conjunction with traditional epidemiological investigation, can be instrumental in revealing routes of transmission and guiding infection control responses.
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Infecção Hospitalar , Infecções por Klebsiella , Infecção Hospitalar/epidemiologia , Detergentes , Surtos de Doenças , Genômica , Humanos , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Klebsiella , Infecções por Klebsiella/epidemiologia , Klebsiella pneumoniae , Filogenia , beta-Lactamases/genéticaRESUMO
PURPOSE: This note describes the performance of a quality assurance (QA) tool built for daily checks of the Gamma Knife's high definition motion management (HDMM) system. METHODS: The tool is a three-dimensional (3D)-printed platform with a raised corner in the center. A reflector post is placed at the corner and the HDMM tool is zeroed to this position. Gage blocks produce very accurate gaps between the post and corner and the HDMM system's readout is compared to the gage block thickness. The HDMM system and tool were tested for noise, stability, reproducibility, linearity, accuracy and overall setup times plus ease of use. RESULTS: The QA tool performed with accuracies better than 0.1 mm. The setup and use of this tool take less than two minutes making it a suitable tool for daily use. CONCLUSION: This QA tool is a cost-effective solution that provides a fast and easy confirmation of the HDMM accuracy, making it suitable for daily QA checks of the HDMM system.
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Radiocirurgia , Humanos , Movimento (Física) , Garantia da Qualidade dos Cuidados de Saúde , Reprodutibilidade dos TestesRESUMO
Sentinel hospital surveillance was instituted in Australia to detect the presence of pandemic group A Streptococcus strains causing scarlet fever. Genomic and phylogenetic analyses indicated the presence of an Australian GAS emm12 scarlet fever isolate related to United Kingdom outbreak strains. National surveillance to monitor this pandemic is recommended.
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Escarlatina/epidemiologia , Escarlatina/microbiologia , Streptococcus pyogenes/classificação , Streptococcus pyogenes/genética , Austrália/epidemiologia , Biologia Computacional/métodos , Surtos de Doenças , Genoma Bacteriano , Genômica/métodos , Humanos , Filogenia , Vigilância da População , Escarlatina/diagnósticoRESUMO
Objectives: To characterize MDR Escherichia coli from bloodstream infections (BSIs) in Australia, New Zealand and Singapore. Methods: We collected third-generation cephalosporin-resistant (3GC-R) E. coli from blood cultures in patients enrolled in a randomized controlled trial from February 2014 to August 2015. WGS was used to characterize antibiotic resistance genes, MLST, plasmids and phylogenetic relationships. Antibiotic susceptibility was determined using disc diffusion and Etest. Results: A total of 70 3GC-R E. coli were included, of which the majority were ST131 (61.4%). BSI was most frequently from a urinary source (69.6%), community associated (62.9%) and in older patients (median age 71 years). The median Pitt score was 1 and ICU admission was infrequent (3.1%). ST131 possessed more acquired resistance genes than non-ST131 (P = 0.003). Clade C1/C2 ST131 predominated (30.2% and 53.5% of ST131, respectively) and these were all ciprofloxacin resistant. All clade A ST131 (n = 6) were community associated. The predominant ESBL types were blaCTX-M (80.0%) and were strongly associated with ST131 (95% carried blaCTX-M), with the majority blaCTX-M-15. Clade C1 was associated with blaCTX-M-14 and blaCTX-M-27, whereas blaCTX-M-15 predominated in clade C2. Plasmid-mediated AmpC genes (mainly blaCMY-2) were frequent (17.1%) but were more common in non-ST131 (P < 0.001) isolates from Singapore and Brisbane. Two strains carried both blaCMY-2 and blaCTX-M. The majority of plasmid replicon types were IncF. Conclusions: In a prospective collection of 3GC-R E. coli causing BSI, community-associated Clade C1/C2 ST131 predominate in association with blaCTX-M ESBLs, although a significant proportion of non-ST131 strains carried blaCMY-2.
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Bacteriemia/epidemiologia , Cefalosporinas/farmacologia , Infecções por Escherichia coli/epidemiologia , Escherichia coli/efeitos dos fármacos , beta-Lactamases/genética , Idoso , Idoso de 80 Anos ou mais , Austrália/epidemiologia , Técnicas de Tipagem Bacteriana , Farmacorresistência Bacteriana/genética , Escherichia coli/classificação , Escherichia coli/genética , Infecções por Escherichia coli/sangue , Feminino , Genoma Bacteriano , Humanos , Masculino , Pessoa de Meia-Idade , Tipagem de Sequências Multilocus , Nova Zelândia/epidemiologia , Filogenia , Prevalência , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Singapura/epidemiologia , Sequenciamento Completo do Genoma , beta-Lactamases/biossínteseRESUMO
Importance: Extended-spectrum ß-lactamases mediate resistance to third-generation cephalosporins (eg, ceftriaxone) in Escherichia coli and Klebsiella pneumoniae. Significant infections caused by these strains are usually treated with carbapenems, potentially selecting for carbapenem resistance. Piperacillin-tazobactam may be an effective "carbapenem-sparing" option to treat extended-spectrum ß-lactamase producers. Objectives: To determine whether definitive therapy with piperacillin-tazobactam is noninferior to meropenem (a carbapenem) in patients with bloodstream infection caused by ceftriaxone-nonsusceptible E coli or K pneumoniae. Design, Setting, and Participants: Noninferiority, parallel group, randomized clinical trial included hospitalized patients enrolled from 26 sites in 9 countries from February 2014 to July 2017. Adult patients were eligible if they had at least 1 positive blood culture with E coli or Klebsiella spp testing nonsusceptible to ceftriaxone but susceptible to piperacillin-tazobactam. Of 1646 patients screened, 391 were included in the study. Interventions: Patients were randomly assigned 1:1 to intravenous piperacillin-tazobactam, 4.5 g, every 6 hours (n = 188 participants) or meropenem, 1 g, every 8 hours (n = 191 participants) for a minimum of 4 days, up to a maximum of 14 days, with the total duration determined by the treating clinician. Main Outcomes and Measures: The primary outcome was all-cause mortality at 30 days after randomization. A noninferiority margin of 5% was used. Results: Among 379 patients (mean age, 66.5 years; 47.8% women) who were randomized appropriately, received at least 1 dose of study drug, and were included in the primary analysis population, 378 (99.7%) completed the trial and were assessed for the primary outcome. A total of 23 of 187 patients (12.3%) randomized to piperacillin-tazobactam met the primary outcome of mortality at 30 days compared with 7 of 191 (3.7%) randomized to meropenem (risk difference, 8.6% [1-sided 97.5% CI, -∞ to 14.5%]; P = .90 for noninferiority). Effects were consistent in an analysis of the per-protocol population. Nonfatal serious adverse events occurred in 5 of 188 patients (2.7%) in the piperacillin-tazobactam group and 3 of 191 (1.6%) in the meropenem group. Conclusions and relevance: Among patients with E coli or K pneumoniae bloodstream infection and ceftriaxone resistance, definitive treatment with piperacillin-tazobactam compared with meropenem did not result in a noninferior 30-day mortality. These findings do not support use of piperacillin-tazobactam in this setting. Trial Registration: anzctr.org.au Identifiers: ACTRN12613000532707 and ACTRN12615000403538 and ClinicalTrials.gov Identifier: NCT02176122.
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Antibacterianos/uso terapêutico , Bacteriemia/mortalidade , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae , Ácido Penicilânico/análogos & derivados , Tienamicinas/uso terapêutico , Adulto , Idoso , Antibacterianos/efeitos adversos , Antibacterianos/farmacologia , Bacteriemia/tratamento farmacológico , Causas de Morte , Ceftriaxona/farmacologia , Farmacorresistência Bacteriana , Escherichia coli/efeitos dos fármacos , Infecções por Escherichia coli/mortalidade , Feminino , Humanos , Infecções por Klebsiella/mortalidade , Klebsiella pneumoniae/efeitos dos fármacos , Masculino , Meropeném , Pessoa de Meia-Idade , Ácido Penicilânico/efeitos adversos , Ácido Penicilânico/uso terapêutico , Piperacilina/efeitos adversos , Piperacilina/uso terapêutico , Combinação Piperacilina e Tazobactam , Tienamicinas/efeitos adversosRESUMO
Uropathogenic Escherichia coli (UPEC) of sequence type 131 (ST131) are a pandemic multidrug resistant clone associated with urinary tract and bloodstream infections. Type 1 fimbriae, a major UPEC virulence factor, are essential for ST131 bladder colonization. The globally dominant sub-lineage of ST131 strains, clade C/H30-R, possess an ISEc55 insertion in the fimB gene that controls phase-variable type 1 fimbriae expression via the invertible fimS promoter. We report that inactivation of fimB in these strains causes altered regulation of type 1 fimbriae expression. Using a novel read-mapping approach based on Illumina sequencing, we demonstrate that 'off' to 'on' fimS inversion is reduced in these strains and controlled by recombinases encoded by the fimE and fimX genes. Unlike typical UPEC strains, the nucleoid-associated H-NS protein does not strongly repress fimE transcription in clade C ST131 strains. Using a genetic screen to identify novel regulators of fimE and fimX in the clade C ST131 strain EC958, we defined a new role for the guaB gene in the regulation of type 1 fimbriae and in colonisation of the mouse bladder. Our results provide a comprehensive analysis of type 1 fimbriae regulation in ST131, and highlight important differences in its control compared to non-ST131 UPEC.
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Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Escherichia coli/efeitos dos fármacos , Escherichia coli/metabolismo , Integrases/genética , Integrases/metabolismo , Receptores Imunológicos/metabolismo , Fatores de Virulência/metabolismo , Animais , DNA Bacteriano/metabolismo , Farmacorresistência Bacteriana Múltipla , Escherichia coli/genética , Infecções por Escherichia coli/microbiologia , Feminino , Proteínas de Fímbrias/metabolismo , Fímbrias Bacterianas/metabolismo , Regulação Bacteriana da Expressão Gênica , Camundongos , Camundongos Endogâmicos C57BL , Escherichia coli Uropatogênica/metabolismo , Fatores de Virulência/genéticaRESUMO
OBJECTIVES: Escherichia coli ST131 is a globally disseminated MDR clone originally identified due to its association with the blaCTX-M-15 gene encoding an ESBL. It is thus assumed that blaCTX-M-15 is the major determinant for resistance to ß-lactam antibiotics in this clone. The complete sequence of EC958, a reference strain for E. coli ST131, revealed that it contains a chromosomally located blaCMY-23 gene with an upstream ISEcp1 element as well as several additional plasmid-encoded ß-lactamase genes. Here, we examined the genetic context of the blaCMY-23 element in EC958 and other E. coli ST131 strains and investigated the contribution of blaCMY-23 to EC958 resistance to a range of ß-lactam antibiotics. METHODS: The genetic context of blaCMY-23 and its associated mobile elements was determined by PCR and sequencing. Antibiotic susceptibility testing was performed using Etests. The activity of the blaCMY-23 promoter was assessed using lacZ reporter assays. Mutations were generated using λ-Red-recombination. RESULTS: The genetic structure of the ISEcp1-IS5-blaCMY-23 mobile element was determined and localized within the betU gene on the chromosome of EC958 and five other E. coli ST131 strains. The transcription of blaCMY-23, driven by a previously defined promoter within ISEcp1, was significantly higher than other ß-lactamase genes and could be induced by cefotaxime. Deletion of the blaCMY-23 gene resulted in enhanced susceptibility to cefoxitin, cefotaxime and ceftazidime. CONCLUSIONS: This is the first known report to demonstrate the chromosomal location of blaCMY-23 in E. coli ST131. In EC958, CMY-23 plays a major role in resistance to third-generation cephalosporins and cephamycins.
Assuntos
Resistência às Cefalosporinas , Proteínas de Escherichia coli/metabolismo , Escherichia coli/efeitos dos fármacos , Escherichia coli/enzimologia , beta-Lactamases/metabolismo , Fusão Gênica Artificial , Cromossomos Bacterianos , DNA Bacteriano/química , DNA Bacteriano/genética , Proteínas de Escherichia coli/genética , Perfilação da Expressão Gênica , Genes Reporter , Sequências Repetitivas Dispersas , Reação em Cadeia da Polimerase , Regiões Promotoras Genéticas , Análise de Sequência de DNA , beta-Galactosidase/análise , beta-Galactosidase/genética , beta-Lactamases/genéticaRESUMO
Many governments employed mandates for COVID-19 vaccines, imposing consequences upon unvaccinated people. Attitudes towards these policies have generally been positive, but little is known about how discourses around them changed as the characteristics of the disease and the vaccinations evolved. Western Australia (WA) employed sweeping COVID-19 vaccine mandates for employment and public spaces whilst the state was closed off from the rest of the country and world, and mostly with no COVID-19 in the community. This article analyses WA public attitudes during the mandate policy lifecycle from speculative to real. Qualitative interview data from 151 adults were analysed in NVivo 20 via a novel chronological analysis anchored in key policy phases: no vaccine mandates, key worker vaccine mandates, vaccine mandates covering 75% of the workforce and public space mandates. Participants justified mandates as essential for border reopening and, less frequently, for goals such as protecting the health system. However, public discourse focusing on 'getting coverage rates up' may prove counter-productive for building support for vaccination; governments should reinforce end goals in public messaging (reducing suffering and saving lives) because such messaging is likely to be more meaningful to vaccination behaviour in the longer term.
RESUMO
Introduction: Community violence is a major cause of injury and death in the United States. Empirical studies have identified that some place-based interventions of urban private places, such as remediations of vacant lots and buildings, are associated with reductions in community violence in surrounding areas. The aim of this study was to examine whether routine maintenance and repair of urban public places (e.g., street construction projects) are also associated with reductions in community violence, proxied by violent crime. Method: This staggered adoption difference-in-difference analysis investigated the association between street construction projects and community violence in New York City from 2010-2019, divided into 40 calendar quarters. The units of analysis were street-quarters (n = 155,280). Intervention street-quarters were those with completed projects in 2010-2019; control streets were those where projects were scheduled but not completed before 2019. The outcome of community violence was proxied by counts of crime and violence incidents reported to the New York Police Department, within street-quarters. Results: There were 79,592 street-quarters with any community violence incidents (51.2%). We found that street construction projects were associated with a decrease in reckless endangerment (ATT = -0.013; 95% CI = -0.021, -0.004), robbery (ATT = -0.035; 95% CI = -0.063, -0.007), and weapons offenses (ATT = -0.016; 95% CI = -0.031, -0.001) occurring on street-quarters. Conclusion: Street construction projects may be yet another type of place-based intervention to reduce community violence.