Systematic disparities in reporting on community firearm violence on local television news in Philadelphia, PA, USA.

Objective: To better understand how community firearm violence (CFV) is communicated to the public, we aimed to identify systematic differences between the characteristics of shooting victims and events covered on television news and all shootings in Philadelphia, PA, a city with escalating CFV incidence. Methods: We compiled a stratified sample of local television news clips covering shootings that occurred in Philadelphia aired on two randomly selected days per month from January-June 2021 (n = 154 clips). We coded the clips to determine demographic and geographic information about the shooting victims and events and then matched coded shootings with corresponding shootings in the Philadelphia police database. We compared characteristics of shooting victims and shooting event locations depicted in television clips (n = 62) with overall characteristics of shootings in Philadelphia during the study period (n = 1082). Results: Compared to all individuals shot, victims whose shootings were covered on local television news more likely to be children and more likely to be shot in a mass shooting. The average median household income of shooting locations featured on television was significantly higher than the median household income across all shooting locations ($60,302 for television shootings vs. $41,233 for all shootings; p = 0.002). Shootings featured on television occurred in areas with lower rates of income inequality and racialized economic segregation compared to all shooting locations. Conclusions: Television news outlets in Philadelphia systematically over-reported shootings of children, mass shootings, and shootings that occurred in neighborhoods with higher median household income, less socioeconomic inequality, and lower rates of racialized economic segregation.

Public health framing of firearm violence on local television news in Philadelphia, PA, USA: a quantitative content analysis.

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.

Interstate Highway Connections and Traced Gun Transfers Between the 48 Contiguous United States.

Importance: Interstate gun flow has critical implications for gun violence prevention, as gun transfers across state lines can undermine local gun control policies. Objective: To identify possible gun trafficking routes along interstate highways in the US. Design, Setting, and Participants: This repeated-measures, ecological, cross-sectional study used data from the Bureau of Alcohol, Tobacco, Firearms and Explosives from January 1, 2010, to December 31, 2019, to examine associations between interstate connections via 13 highways that each spanned at least 1000 miles and interstate traced gun transfer counts for the 48 contiguous United States. Analyses were completed in November 2023. Exposures: Characteristics of the origin states and the transportation connections between the destination state and the origin states. Main Outcomes and Measures: The main outcome was the total count of guns used in crimes in each destination state per year that were originally purchased in the origin state. Bayesian conditional autoregressive Poisson models were used to examine associations between the count of guns used in crime traced to interstate purchases and interstate highway connections between origin and destination states. Results: Between 2010 and 2019, 526 801 guns used in crimes in the contiguous 48 states were traced to interstate purchases. Northbound gun transfers along the Interstate 95 corridor were greater than expected to New Jersey (incidence rate ratio [IRR], 2.80; 95% credible interval [CrI], 1.01-7.68) and Maryland (IRR, 3.07; 95% CrI, 1.09-8.61); transfers were similarly greater along Interstate 15 southbound, Interstate 25 southbound, Interstate 35 southbound, Interstate 75 northbound and southbound, Interstate 10 westbound, and Interstate 20 eastbound and westbound. Conclusions and Relevance: This repeated-measures, ecological, cross-sectional study identified that guns used in crimes traced to interstate purchases moved routinely between states along multiple major transportation routes. Interstate gun transfers are a major contributor to gun crime, injury, and death in the US. National policies and interstate cooperation are needed to address this issue.

Trends in police complaints and arrests on New York City subways, 2018 to 2023: an interrupted time-series analysis.

BACKGROUND: Public transportation use is influenced by perceptions of safety. Concerns related to crime on New York City (NYC) transit have risen following NYC's COVID-19 pandemic state of emergency declaration in 2020, leading to declines in subway ridership. In response, the most recent mayoral administration implemented a Subway Safety Plan in 2022. This study aimed to quantify the effects of the COVID-19 pandemic and the Subway Safety Plan on rates of complaints to and arrests by the New York City Police Department (NYPD) Transit Bureau. METHODS: Using publicly available data on complaints and arrests, we conducted interrupted time-series analyses using autoregressive integrated moving average models applied to monthly data for the period from September 2018 to August 2023. We estimated changes in the rates of complaints to and arrests by the NYPD Transit Bureau before and after: (1) the COVID-19 pandemic state of emergency declaration (i.e., March 2020), and (2) the announcement of the Subway Safety Plan (i.e., February 2022). We also examined trends by complaint and arrest type as well as changes in proportion of arrests by demographic and geographic groups. RESULTS: After the COVID-19 pandemic declaration, there was an 84% increase (i.e., an absolute increase of 6.07 per 1,000,000 riders, CI 1.42, 10.71) in complaints to the NYPD Transit Bureau, including a 99% increase (0.91 per 1,000,000 riders, CI 0.42, 1.41) in complaints for assault and a 125% increase in complaints for harassment (0.94 per 1,000,000 riders, CI 0.29, 1.60). Following the Subway Safety Plan there was an increase in the rate of arrests for harassment (0.004 per 1,000,000 riders, CI 0.001, 0.007), as well as decreases in the proportion of arrests for individuals racialized as White (- 0.02, CI - 0.04, - 0.01) and proportion of arrests in the borough of Manhattan (- 0.13, CI - 0.17, - 0.09). CONCLUSIONS: The increased rates of complaints to the NYPD Transit Bureau following the onset of the COVID-19 pandemic remained elevated following the enactment of the Subway Safety Plan. Further evaluation efforts can help identify effective means of promoting safety on public transportation.

Defining Spatial Epidemiology: A Systematic Review and Re-Orientation.

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 papers 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, intervention) and recorded the unit of analysis (i.e., individual vs. ecological). We additionally examined papers coded as analytic ecologic studies using scales for lexical content. RESULTS: A total of 482 papers 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 (IRR =1.3, 95%CI: 1.1, 1.5) and causal inference (IRR =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.

HAIviz: an interactive dashboard for visualising and integrating healthcare-associated genomic epidemiological data.

Existing tools for phylogeographic and epidemiological visualisation primarily provide a macro-geographic view of epidemic and pandemic transmission events but offer little support for detailed investigation of outbreaks in healthcare settings. Here, we present HAIviz, an interactive web-based application designed for integrating and visualising genomic epidemiological information to improve the tracking of healthcare-associated infections (HAIs). HAIviz displays and links the outbreak timeline, building map, phylogenetic tree, patient bed movements, and transmission network on a single interactive dashboard. HAIviz has been developed for bacterial outbreak investigations but can be utilised for general epidemiological investigations focused on built environments for which visualisation to customised maps is required. This paper describes and demonstrates the application of HAIviz for HAI outbreak investigations.

Antibiotic resistance determination using Enterococcus faecium whole-genome sequences: a diagnostic accuracy study using genotypic and phenotypic data.

BACKGROUND: DNA sequencing could become an alternative to in vitro antibiotic susceptibility testing (AST) methods for determining antibiotic resistance by detecting genetic determinants associated with decreased antibiotic susceptibility. Here, we aimed to assess and improve the accuracy of antibiotic resistance determination from Enterococcus faecium genomes for diagnosis and surveillance purposes. METHODS: In this retrospective diagnostic accuracy study, we first conducted a literature search in PubMed on Jan 14, 2021, to compile a catalogue of genes and mutations predictive of antibiotic resistance in E faecium. We then evaluated the diagnostic accuracy of this database to determine susceptibility to 12 different, clinically relevant antibiotics using a diverse population of 4382 E faecium isolates with available whole-genome sequences and in vitro culture-based AST phenotypes. Isolates were obtained from various sources in 11 countries worldwide between 2000 and 2018. We included isolates tested with broth microdilution, Vitek 2, and disc diffusion, and antibiotics with at least 50 susceptible and 50 resistant isolates. Phenotypic resistance was derived from raw minimum inhibitory concentrations and measured inhibition diameters, and harmonised primarily using the breakpoints set by the European Committee on Antimicrobial Susceptibility Testing. A bioinformatics pipeline was developed to process raw sequencing reads, identify antibiotic resistance genetic determinants, and report genotypic resistance. We used our curated database, as well as ResFinder, AMRFinderPlus, and LRE-Finder, to assess the accuracy of genotypic predictions against phenotypic resistance. FINDINGS: We curated a catalogue of 228 genetic markers involved in resistance to 12 antibiotics in E faecium. Very accurate genotypic predictions were obtained for ampicillin (sensitivity 99·7% [95% CI 99·5-99·9] and specificity 97·9% [95·8-99·0]), ciprofloxacin (98·0% [96·4-98·9] and 98·8% [95·9-99·7]), vancomycin (98·8% [98·3-99·2] and 98·8% [98·0-99·3]), and linezolid resistance (after re-testing false negatives: 100·0% [90·8-100·0] and 98·3% [97·8-98·7]). High sensitivity was obtained for tetracycline (99·5% [99·1-99·7]), teicoplanin (98·9% [98·4-99·3]), and high-level resistance to aminoglycosides (97·7% [96·6-98·4] for streptomycin and 96·8% [95·8-97·5] for gentamicin), although at lower specificity (60-90%). Sensitivity was expectedly low for daptomycin (73·6% [65·1-80·6]) and tigecycline (38·3% [27·1-51·0]), for which the genetic basis of resistance is not fully characterised. Compared with other antibiotic resistance databases and bioinformatic tools, our curated database was similarly accurate at detecting resistance to ciprofloxacin and linezolid and high-level resistance to streptomycin and gentamicin, but had better sensitivity for detecting resistance to ampicillin, tigecycline, daptomycin, and quinupristin-dalfopristin, and better specificity for ampicillin, vancomycin, teicoplanin, and tetracycline resistance. In a validation dataset of 382 isolates, similar or improved diagnostic accuracies were also achieved. INTERPRETATION: To our knowledge, this work represents the largest published evaluation to date of the accuracy of antibiotic susceptibility predictions from E faecium genomes. The results and resources will facilitate the adoption of whole-genome sequencing as a tool for the diagnosis and surveillance of antimicrobial resistance in E faecium. A complete characterisation of the genetic basis of resistance to last-line antibiotics, and the mechanisms mediating antibiotic resistance silencing, are needed to close the remaining sensitivity and specificity gaps in genotypic predictions. FUNDING: Wellcome Trust, UK Department of Health, British Society for Antimicrobial Chemotherapy, Academy of Medical Sciences and the Health Foundation, Medical Research Council Newton Fund, Vietnamese Ministry of Science and Technology, and European Society of Clinical Microbiology and Infectious Disease.

West Australian parents' views on vaccinating their children against COVID-19: a qualitative study.

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.

Long-read sequencing reveals genomic diversity and associated plasmid movement of carbapenemase-producing bacteria in a UK hospital over 6 years.

Healthcare-associated infections (HCAIs) affect the most vulnerable people in society and are increasingly difficult to treat in the face of mounting antimicrobial resistance (AMR). Routine surveillance represents an effective way of understanding the circulation and burden of bacterial resistance and transmission in hospital settings. Here, we used whole-genome sequencing (WGS) to retrospectively analyse carbapenemase-producing Gram-negative bacteria from a single hospital in the UK over 6 years (n=165). We found that the vast majority of isolates were either hospital-onset (HAI) or HCAI. Most carbapenemase-producing organisms were carriage isolates, with 71 % isolated from screening (rectal) swabs. Using WGS, we identified 15 species, the most common being Escherichia coli and Klebsiella pneumoniae. Only one significant clonal outbreak occurred during the study period and involved a sequence type (ST)78 K. pneumoniae carrying bla NDM-1 on an IncFIB/IncHI1B plasmid. Contextualization with public data revealed little evidence of this ST outside of the study hospital, warranting ongoing surveillance. Carbapenemase genes were found on plasmids in 86 % of isolates, the most common types being bla NDM- and bla OXA-type alleles. Using long-read sequencing, we determined that approximately 30 % of isolates with carbapenemase genes on plasmids had acquired them via horizontal transmission. Overall, a national framework to collate more contextual genomic data, particularly for plasmids and resistant bacteria in the community, is needed to better understand how carbapenemase genes are transmitted in the UK.

Clinical utility of whole-genome DNA methylation profiling as a primary molecular diagnostic assay for central nervous system tumors-A prospective study and guidelines for clinical testing.

Background: Central nervous system (CNS) cancer is the 10th leading cause of cancer-associated deaths for adults, but the leading cause in pediatric patients and young adults. The variety and complexity of histologic subtypes can lead to diagnostic errors. DNA methylation is an epigenetic modification that provides a tumor type-specific signature that can be used for diagnosis. Methods: We performed a prospective study using DNA methylation analysis as a primary diagnostic method for 1921 brain tumors. All tumors received a pathology diagnosis and profiling by whole genome DNA methylation, followed by next-generation DNA and RNA sequencing. Results were stratified by concordance between DNA methylation and histopathology, establishing diagnostic utility. Results: Of the 1602 cases with a World Health Organization histologic diagnosis, DNA methylation identified a diagnostic mismatch in 225 cases (14%), 78 cases (5%) did not classify with any class, and in an additional 110 (7%) cases DNA methylation confirmed the diagnosis and provided prognostic information. Of 319 cases carrying 195 different descriptive histologic diagnoses, DNA methylation provided a definitive diagnosis in 273 (86%) cases, separated them into 55 methylation classes, and changed the grading in 58 (18%) cases. Conclusions: DNA methylation analysis is a robust method to diagnose primary CNS tumors, improving diagnostic accuracy, decreasing diagnostic errors and inconclusive diagnoses, and providing prognostic subclassification. This study provides a framework for inclusion of DNA methylation profiling as a primary molecular diagnostic test into professional guidelines for CNS tumors. The benefits include increased diagnostic accuracy, improved patient management, and refinements in clinical trial design.

Amino acid digestibility and nitrogen-corrected true metabolizable energy of mildly cooked human-grade vegan dog foods using the precision-fed cecectomized and conventional rooster assays.

The pet food market is constantly changing and adapting to meet the needs and desires of pets and their owners. One trend that has been growing in popularity lately is the feeding of fresh, human-grade foods. Human-grade pet foods contain ingredients that have all been stored, handled, processed, and transported in a manner that complies with regulations set for human food production. While most human-grade pet foods are based on animal-derived ingredients, vegan options also exist. To our knowledge, no in vivo studies have been conducted to analyze the performance of human-grade vegan diets. Therefore, the objective of this study was to investigate the amino acid (AA) digestibility and nitrogen-corrected true metabolizable energy (TME n ) of mildly cooked human-grade vegan dog foods using precision-fed cecectomized rooster and conventional rooster assays. Three commercial dog foods were tested. Two were mildly cooked human-grade vegan dog diets (Bramble Cowbell diet (BC); Bramble roost diet (BR)), while the third was a chicken-based extruded dog diet (chicken and brown rice recipe diet (CT)). Prior to the rooster assays, both mildly cooked diets were lyophilized, and then all three diets were ground. Diets were fed to cecectomized roosters to determine AA digestibility, while conventional roosters were used to determine TME n . All data were analyzed using the mixed models procedure of SAS (version 9.4). The majority of indispensable and dispensable AA across all diets had digestibilities higher than 80%, with a few exceptions (BC: histidine, lysine, threonine, and valine; BR: histidine). The only difference in indispensable AA digestibility among diets was observed with tryptophan, with its digestibility being higher (P = 0.0163) in CT than in BC. TME n values were higher (P = 0.006) in BC and BR (4.55 and 4.66 kcal/g dry matter, respectively) than that in CT (3.99 kcal/g dry matter). The TME n /GE was also higher (P = 0.0193) in BR than in CT. Metabolizable energy (ME) estimates using Atwater factors accurately estimated the energy content of CT, but modified Atwater factors and the predictive equations for ME recommended by the National Research Council underestimated energy content. All calculations underestimated the measured TME n values of BC and BR, with Atwater factors being the closest. Although testing in dogs is required, these data suggest that mildly cooked human-grade vegan dog diets are well-digested. Moreover, TME n data suggest that existing methods and equations underestimate the ME of the mildly cooked human-grade vegan foods tested.

Apparent total tract macronutrient digestibility of mildly cooked human-grade vegan dog foods and their effects on the blood metabolites and fecal characteristics, microbiota, and metabolites of adult dogs.

Vegan, mildly cooked, and human-grade dog foods are becoming more popular, as beliefs and views of pet owners change. To our knowledge, however, dog studies have not examined the digestibility of commercial vegan diets. Therefore, the objective of this study was to determine the apparent total tract digestibility (ATTD) of mildly cooked human-grade vegan dog foods and their effects on blood metabolites and fecal microbiota, characteristics, and metabolites of adult dogs consuming them. Three commercial dog foods were tested. Two were mildly cooked human-grade vegan dog diets, while the third was a chicken-based extruded dog diet. Twelve healthy adult female beagles (7.81 ± 0.65 kg; 7.73 ± 1.65 yr) were used in a replicated 3 × 3 Latin Square design. The study consisted of three experimental periods, with each composed of a 7 d diet adaptation phase, 15 d of consuming 100% of the diet, a 5 d phase for fecal collection for ATTD measurement, and 1 d for blood collection for serum chemistry and hematology. During the fecal collection period, a fresh sample was collected for fecal scoring and dry matter, pH, metabolite, and microbiota measurements. All data were analyzed using the Mixed Models procedure of SAS (version 9.4). All three diets were shown to be highly digestible, with all macronutrients having digestibility values above 80%. The vegan diets had higher (P < 0.001) ATTD of fat, but lower (P < 0.05) ATTD of organic matter than the extruded diet. Dogs consuming the vegan diets had lower circulating cholesterol (P < 0.001), triglyceride (P < 0.001), and platelet (P < 0.009) concentrations and lower (P < 0.010) blood neutrophil percentages than dogs consuming the extruded diet. Dogs consuming vegan diets had lower (P < 0.001) fecal dry matter percentages, lower (P < 0.001) fecal phenol and indole concentrations, and higher (P = 0.05) fecal short-chain fatty acid concentrations than those consuming the extruded diet. Fecal bacterial alpha and beta diversities were not different (P > 0.05) among diets, but dogs consuming vegan diets had altered (P < 0.05) relative abundances of nearly 20 bacterial genera when compared with those consuming the extruded diet. In conclusion, the mildly cooked human-grade vegan dog foods tested in this study performed well, resulting in desirable fecal characteristics, ATTD, and serum chemistries. The vegan diets tested also led to positive changes to serum lipids and fecal metabolites, and interesting changes to the fecal microbial community.

Vegan, mildly cooked, and human-grade dog foods are increasing in popularity, but few studies have been performed to examine their performance. Our objective was to determine the apparent total tract digestibility (ATTD) of mildly cooked human-grade vegan dog foods and their effects on blood metabolites and fecal microbiota, characteristics, and metabolites of dogs. Two mildly cooked human-grade vegan dog diets and a chicken-based extruded dog diet were tested using 12 healthy adult dogs in a replicated 3 × 3 Latin Square design. All diets were highly digestible, with all macronutrients having digestibility values >80%. Vegan diets had higher ATTD of fat, but lower ATTD of organic matter than the extruded diet. Dogs consuming vegan diets had lower circulating cholesterol, triglycerides, platelets, and neutrophils than dogs consuming the extruded diet. Dogs consuming vegan diets had lower fecal dry matter percentages and phenol and indole concentrations, and higher fecal short-chain fatty acid concentrations than those consuming the extruded diet. Finally, ~20 bacterial genera were altered between dogs consuming vegan and extruded diets. In conclusion, the mildly cooked human-grade vegan dog foods tested performed well, resulting in desirable fecal characteristics, high ATTD, adequate serum chemistries, positive changes to serum lipids and fecal metabolites, and interesting changes to fecal microbiota.

'COVID Is Coming, and I'm Bloody Scared': How Adults with Co-Morbidities' Threat Perceptions of COVID-19 Shape Their Vaccination Decisions.

Adults with comorbidities have faced a high risk from COVID-19 infection. However, Western Australia experienced relatively few infections and deaths from 2020 until early 2022 compared with other OECD countries, as hard border policies allowed for wide-scale vaccination before mass infections began. This research investigated the thoughts, feelings, risk perceptions, and practices of Western Australian adults with comorbidities aged 18-60 years in regard to COVID-19 disease and COVID-19 vaccines. We conducted 14 in-depth qualitative interviews between January and April 2022, just as the disease was starting to circulate. We coded results inductively and deductively, combining the Extended Parallel Process Model (EPPM) and vaccine belief models. Non-hesitant participants believed COVID-19 vaccines were safe and effective at mitigating COVID-19's threat and subsequently got vaccinated. Vaccine hesitant participants were less convinced the disease was severe or that they were susceptible to it; they also did not consider the vaccines to be sufficiently safe. Yet, for some hesitant participants, the exogenous force of mandates prompted vaccination. This work is important to understand how people's thoughts and feelings about their comorbidities and risks from COVID-19 influence vaccine uptake and how mandatory policies can affect uptake in this cohort.

Genomic characterisation of multidrug-resistant Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii in two intensive care units in Hanoi, Viet Nam: a prospective observational cohort study.

BACKGROUND: Viet Nam has high rates of antimicrobial resistance (AMR) but little capacity for genomic surveillance. This study used whole genome sequencing to examine the prevalence and transmission of three key AMR pathogens in two intensive care units (ICUs) in Hanoi, Viet Nam. METHODS: A prospective surveillance study of all adults admitted to ICUs at the National Hospital for Tropical Diseases and Bach Mai Hospital was done between June 19, 2017, and Jan 16, 2018. Clinical and environmental samples were cultured on selective media, characterised with MALDI TOF mass spectrometry, and sequenced with Illumina. Phylogenies based on the de-novo assemblies (SPAdes) were constructed with MAFFT (PARsnp), Gubbins, and RAxML. Resistance genes were detected with Abricate against the US National Center for Biotechnology Information database. FINDINGS: 3153 Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii isolates from 369 patients were analysed. Phylogenetic analysis revealed predominant lineages within A baumannii (global clone 2, sequence types ST2 and ST571) and K pneumoniae (ST15, ST16, ST656, ST11, and ST147) isolates. Isolation from stool was most common with E coli (87·0%) followed by K pneumoniae (62·5%). Of the E coli, 85·0% carried a blaCTX-M variant, while 81·8% of K pneumoniae isolates carried blaNDM (54·4%), or blaKPC (45·1%), or both. Transmission analysis with single nucleotide polymorphisms identified 167 clusters involving 251 (68%) of 369 patients, in some cases involving patients from both ICUs. There were no clear differences between the lineages or AMR genes recovered between the two ICUs. INTERPRETATION: This study represents the largest prospective surveillance study of key AMR pathogens in Vietnamese ICUs. Clusters of closely related isolates in patients across both ICUs suggests recent transmission before ICU admission in other health-care settings or in the community. FUNDING: UK Medical Research Council Newton Fund, Viet Nam Ministry of Science and Technology, Wellcome Trust, Academy of Medical Sciences, Health Foundation, and UK National Institute for Health and Care Research Cambridge Biomedical Research Centre.

Western Australian health care workers' views on mandatory COVID-19 vaccination for the workplace.

Background: Health care workers (HCWs) are at an increased risk of catching and spreading Coronavirus Disease 2019 (COVID-19) compared with the general community, putting health systems at risk. Several jurisdictions globally have mandated or are looking to mandate COVID-19 vaccines for this cohort, but little is known about the acceptability of this measure, especially in different contexts, and there is little qualitative data to explore nuance, depth, and the reasons behind HCWs' opinions. Methods: In-depth semi-structured qualitative interviews were undertaken with 39 HCWs in Western Australia (WA) between February-August 2021, ascertaining their views on the prospective introduction and implementation of mandates for COVID-19 vaccines. Data were thematically analysed using NVivo 20. Results: There was broad support for COVID-19 vaccine mandates for HCWs amongst our participants, but also different views about what such a mandate would mean (redeployment versus termination) and how it would impact the rest of the workforce. One vaccine hesitant participant said that mandates would be their prompt to get vaccinated. Other participants invoked an informal code whereby HCWs have an obligation to be seen to support vaccination and to protect public health more broadly. However, they also raised concerns about implementation and procedural and policy fairness. Conclusion: Policymakers should consider how to mobilise the informal code of health promotion and public health support if introducing mandates. They should also consider whether HCWs will bring the same attitudes and approaches to mandates for additional vaccine doses.

COVID-19 Vaccine Mandates: Attitudes and Effects on Holdouts in a Large Australian University Population.

Many governments and institutions mandated COVID-19 vaccines. In late 2021, we sought to ascertain the perspectives of staff and students from The University of Western Australia about the State or the University mandating COVID-19 vaccines. The survey captured vaccination status and intentions along with attitudes towards mandates and potential types of exemptions with 2878 valid responses which were quantitatively analysed and 2727 which were qualitatively analysed. The study found generally high levels of vaccination or intent, and strong support for mandates, underpinned by beliefs that vaccination is a moral duty and that mandates make campus feel safer. These sentiments were not more prevalent amongst individuals with comorbidities; often healthy individuals supported mandates to reduce their risk of transmitting disease to vulnerable family members. Individuals with comorbidities were, however, more supportive of excluding the unvaccinated from campus. Most opponents were unvaccinated, and many indicated that mandate policies would backfire, making them less likely to vaccinate. Despite the strong overall support, 41% of respondents did not want to see non-compliant staff or students lose their positions, and only 35% actively sought this. Institutions or governments introducing mandates should emphasise community concerns about catching COVID-19 and becoming sick or transmitting the disease to vulnerable loved ones.

Transcriptomic landscape of granulosa cells and peripheral blood mononuclear cells in women with PCOS compared to young poor responders and women with normal response.

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.

Differential Afa/Dr Fimbriae Expression in the Multidrug-Resistant Escherichia coli ST131 Clone.

Many antibiotic resistant uropathogenic Escherichia coli (UPEC) strains belong to clones defined by their multilocus sequence type (ST), with ST131 being the most dominant. Although we have a good understanding of resistance development to fluoroquinolones and third-generation cephalosporins by ST131, our understanding of the virulence repertoire that has contributed to its global dissemination is limited. Here we show that the genes encoding Afa/Dr fimbriae, a group of adhesins strongly associated with UPEC that cause gestational pyelonephritis and recurrent cystitis, are found in approximately one third of all ST131 strains. Sequence comparison of the AfaE adhesin protein revealed a unique allelic variant carried by 82.9% of afa-positive ST131 strains. We identify the afa regulatory region as a hotspot for the integration of insertion sequence (IS) elements, all but one of which alter afa transcription. Close investigation demonstrated that the integration of an IS1 element in the afa regulatory region leads to increased expression of Afa/Dr fimbriae, promoting enhanced adhesion to kidney epithelial cells and suggesting a mechanism for altered virulence. Finally, we provide evidence for a more widespread impact of IS1 on ST131 genome evolution, suggesting that IS dynamics contribute to strain level microevolution that impacts ST131 fitness. IMPORTANCE E. coli ST131 is the most common antibiotic resistant UPEC clone associated with human urinary tract and bloodstream infections. Understanding the features of ST131 that have driven its global dissemination remains a critical priority if we are to counter its increasing antibiotic resistance. Here, we utilized a large collection of ST131 isolates to investigate the prevalence, regulation, and function of Afa/Dr fimbriae, a well-characterized UPEC colonization and virulence factor. We show that the afa genes are found frequently in ST131 and demonstrate how the integration of IS elements in the afa regulatory region modulates Afa expression, presenting an example of altered virulence capacity. We also exploit a curated set of ST131 genomes to map the integration of the antibiotic resistance-associated IS1 element in the ST131 pangenome, providing evidence for its widespread impact on ST131 genome evolution.

Does a major change to a COVID-19 vaccine program alter vaccine intention? A qualitative investigation.

BACKGROUND: On 8th April 2021, the Australian Technical Advisory Group on Immunisation (ATAGI) made the Pfizer-BioNtech (Comirnaty) vaccine the "preferred" vaccine for adults in Australia aged < 50 years due to a risk of thrombosis with thrombocytopenia syndrome (TTS) following AstraZeneca vaccination. We sought to understand whether this impacted COVID-19 vaccine intentions. METHOD: We undertook qualitative interviews from February - April 2021 before and after the program change with 28 adults in Perth, Western Australia. Using our COVID-19 vaccine intentions model, we assessed changes in participants' COVID-19 vaccine intention before and after the program change. Participants were classified as 1) 'acceptors': no concerns about COVID-19 vaccine safety, efficacy, access and would accept whatever vaccine is offered, 2) 'cautious acceptors': some concerns and would prefer a particular vaccine brand but would accept whatever is offered, 3) 'Wait awhile': for more data, easier access, for another vaccine brand, a greater perceived COVID-19 threat or until mandatory, or 4) 'refuser': no intention to vaccinate due to concerns about safety and/or efficacy. RESULTS: Before the change, 7/18 of those aged < 50 years were 'acceptors,' 10/18 were 'cautious acceptors' and 1/18 was 'wait awhile.' Overall, 14/18 participants had the same COVID-19 vaccine intention after the change; 4/18 became more concerned. For those aged ≥ 50 years and before the change, 5/10 were 'acceptors' and 5/10 were 'cautious acceptors.' After the change, 8/10 still had the same COVID-19 vaccine intention; 2/10 became more cautious. The major concern before the program change was COVID-19 vaccines having different vaccine efficacy; the concern pivoted to safety. CONCLUSION: The majority of participants were 'cautious acceptors' who intended on being vaccinated; many had this intention before and after the program change. The Australian government, health care providers and media need to better address COVID-19 vaccine concerns to assist those with COVID-19 vaccine intentions receive a vaccine.

COVID-19 vaccine Mandates: An Australian attitudinal study.

BACKGROUND: The rollout of vaccines against COVID-19 is prompting governments and the private sector to adopt mandates. However, there has been little conceptual analysis of the types of mandates available, nor empirical analysis of how the public thinks about different mandates and why. Our conceptual study examines available instruments, how they have been implemented pre-COVID, and their use for COVID-19 globally. Then, our qualitative study reports the acceptability of such measures in Western Australia, which has experienced very limited community transmission, posing an interesting scenario for vaccine acceptance and acceptability of measures to enforce it. METHOD: Our conceptual study developed categories of mandates from extant work, news reports, and legislative interventions globally. Then, our empirical study asked 44 West Australians about their attitudes towards potential mandatory policies, with data analysed using NVivo 12. RESULTS: Our novel studies contribute richness and depth to emerging literature on the types and varying acceptability of vaccine requirements. Participants demonstrated tensions and confusion about whether instruments were incentives or punishments, and many supported strong consequences for non-vaccination even if they ostensibly opposed mandates. Those attached to restrictions for disease prevention were most popular. There were similar degrees of support for mandates imposed by employers or businesses, with participants showing little concern for potential issues of accountability linked to public health decisions delegated to the private sector. Participants mostly supported tightly regulated medical exemptions granted by specialists, with little interest in religious or personal belief exemptions. CONCLUSION: Our participants are used to being governed by vaccine mandates, and now by rigorous lockdown and travel restrictions that have ensured limited local COVID-19 disease and transmission. These factors appear influential in their general openness to COVID-19 vaccine mandates, especially when linked explicitly to the prevention of disease in high-risk settings.