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The circumstances under which airborne transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might occur are uncertain (1,2). Previous cluster reports have suggested involvement of airborne transmission (3,4), but [...]

Abstract Background Anti-malarial drug resistance remains a key concern for the global fight against malaria. In Ghana sulfadoxine-pyrimethamine (SP) is used for intermittent preventive treatment of malaria in pregnancy and combined with amodiaquine for Seasonal Malaria Chemoprevention (SMC) during the high malaria season. Thus, surveillance of molecular markers of SP resistance is important to guide decision-making for these interventions in Ghana. Methods A total of 4469 samples from uncomplicated malaria patients collected from 2009 to 2018 was submitted to the Wellcome Trust Sanger Institute, UK for DNA sequencing using MiSeq. Genotypes were successfully translated into haplotypes in 2694 and 846 mono infections respectively for pfdhfr and pfdhps genes and the combined pfhdfr/pfdhps genes across all years. Results At the pfdhfr locus, a consistently high (> 60%) prevalence of parasites carrying triple mutants (IRNI) were detected from 2009 to 2018. Two double mutant haplotypes (NRNI and ICNI) were found, with haplotype NRNI having a much higher prevalence (average 13.8%) than ICNI (average 3.2%) across all years. Six pfdhps haplotypes were detected. Of these, prevalence of five fluctuated in a downward trend over time from 2009 to 2018, except a pfdhps double mutant (AGKAA), which increased consistently from 2.5% in 2009 to 78.2% in 2018. Across both genes, pfdhfr/pfdhps combined triple (NRNI + AAKAA) mutants were only detected in 2009, 2014, 2015 and 2018, prevalence of which fluctuated between 3.5 and 5.5%. The combined quadruple (IRNI + AAKAA) genotype increased in prevalence from 19.3% in 2009 to 87.5% in 2011 before fluctuating downwards to 19.6% in 2018 with an average prevalence of 37.4% within the nine years. Prevalence of parasites carrying the quintuple (IRNI + AGKAA or SGEAA) mutant haplotypes, which are highly refractory to SP increased over time from 14.0% in 2009 to 89.0% in 2016 before decreasing to 78.9 and 76.6% in 2017 and 2018 respectively. Though quintuple mutants are rising in prevalence in both malaria seasons, together these combined genotypes vary significantly within season but not between seasons. Conclusions Despite high prevalence of pfdhfr triple mutants and combined pfdhfr/pfdhps quadruple and quintuple mutants in this setting SP may still be efficacious. These findings are significant as they highlight the need to continuously monitor SP resistance, particularly using deep targeted sequencing to ascertain changing resistance patterns.

Introduction Social deprivation is a known determinant of health and related behaviors. Many studies have linked socioeconomic factors to secondhand smoke (SHS) exposure. However, no studies have examined the relationship between social deprivation and SHS exposure. This study examined whether contextual social deprivation – variously based on living in a house without a car, that was overcrowded, or had an unemployed member (s) – had an independent association with SHS exposure at both individual and regional levels among Chinese residents. Methods A cross-sectional multistage sampling design was utilized to interview subjects from 6 selected cities in China. A standardized questionnaire selected sociodemographic characteristics, contextual social deprivation and SHS exposure. Multilevel logistic regression models were used to assess the association between social deprivation and SHS exposure. Results A total of 5782 valid questionnaires were collected in this study. Among 2930 non-smokers, the SHS exposure prevalence was 21.9% (95% CI: 19.5– 24.30). Multilevel logistic regression showed a negative association between household income, regional GDP, and SHS exposure, respectively, and positive associations between contextual social deprivation and SHS exposure. Conclusions Findings support the central proposition that contextual social deprivation must be factored into SHS exposure messages. Our research underscores the importance of reducing health inequality in controlling SHS exposure.

Invasive bacterial disease is a major cause of morbidity and mortality in African children. Despite being caused by diverse pathogens, children with sepsis are clinically indistinguishable from one another. In spite of this, most genetic susceptibility loci for invasive infection that have been discovered to date are pathogen specific and are not therefore suggestive of a shared genetic architecture of bacterial sepsis. Here, we utilise probabilistic diagnostic models to identify children with a high probability of invasive bacterial disease among critically unwell Kenyan children with Plasmodium falciparum parasitaemia. We construct a joint dataset including 1445 bacteraemia cases and 1143 severe malaria cases, and population controls, among critically unwell Kenyan children that have previously been genotyped for human genetic variation. Using these data, we perform a cross-trait genome-wide association study of invasive bacterial infection, weighting cases according to their probability of bacterial disease. In doing so, we identify and validate a novel risk locus for invasive infection secondary to multiple bacterial pathogens, that has no apparent effect on malaria risk. The locus identified modifies splicing of BIRC6 in stimulated monocytes, implicating regulation of apoptosis and autophagy in the pathogenesis of sepsis in Kenyan children.

BackgroundLow frequency intrahost single nucleotide variants (iSNVs) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) have been increasingly recognised as predictive indicators of positive selection. Particularly as growing numbers of SARS-CoV-2 variants of interest (VOI) and concern (VOC) emerge. However, the dynamics of subgenomic RNA (sgRNA) expression and its impact on genomic diversity and infection outcome remain poorly understood. This study aims to investigate and quantify iSNVs and sgRNA expression in single and longitudinally sampled cohorts over the course of mild and severe SARS-CoV-2 infection, benchmarked against an in vitro infection model.MethodsTwo clinical cohorts of SARS-CoV-2 positive cases in New South Wales, Australia collected between March 2020 and August 2021 were sequenced. Longitudinal samples from cases hospitalised due to SARS-CoV-2 infection (severe) (n = 16) were analysed and compared with cases that presented with SARS-CoV-2 symptoms but were not hospitalised (mild) (n = 23). SARS-CoV-2 genomic diversity profiles were also examined from daily sampling of culture experiments for three SARS-CoV-2 variants (Lineage A, B.1.351, and B.1.617.2) cultured in VeroE6 C1008 cells (n = 33).ResultsIntrahost single nucleotide variants were detected in 83% (19/23) of the mild cohort cases and 100% (16/16) of the severe cohort cases. SNP profiles remained relatively fixed over time, with an average of 1.66 SNPs gained or lost, and an average of 4.2 and 5.9 low frequency variants per patient were detected in severe and mild infection, respectively. sgRNA was detected in 100% (25/25) of the mild genomes and 92% (24/26) of the severe genomes. Total sgRNA expressed across all genes in the mild cohort was significantly higher than that of the severe cohort. Significantly higher expression levels were detected in the spike and the nucleocapsid genes. There was significantly less sgRNA detected in the culture dilutions than the clinical cohorts.Discussion and ConclusionThe positions and frequencies of iSNVs in the severe and mild infection cohorts were dynamic overtime, highlighting the importance of continual monitoring, particularly during community outbreaks where multiple SARS-CoV-2 variants may co-circulate. sgRNA levels can vary across patients and the overall level of sgRNA reads compared to genomic RNA can be less than 1%. The relative contribution of sgRNA to the severity of illness warrants further investigation given the level of variation between genomes. Further monitoring of sgRNAs will improve the understanding of SARS-CoV-2 evolution and the effectiveness of therapeutic and public health containment measures during the pandemic.

As many malaria-endemic countries move towards elimination of Plasmodium falciparum, the most virulent human malaria parasite, effective tools for monitoring malaria epidemiology are urgent priorities. P. falciparum population genetic approaches offer promising tools for understanding transmission and spread of the disease, but a high prevalence of multi-clone or polygenomic infections can render estimation of even the most basic parameters, such as allele frequencies, challenging. A previous method, COIL, was developed to estimate complexity of infection (COI) from single nucleotide polymorphism (SNP) data, but relies on monogenomic infections to estimate allele frequencies or requires external allele frequency data which may not available. Estimates limited to monogenomic infections may not be representative, however, and when the average COI is high, they can be difficult or impossible to obtain. Therefore, we developed THE REAL McCOIL, Turning HEterozygous SNP data into Robust Estimates of ALelle frequency, via Markov chain Monte Carlo, and Complexity Of Infection using Likelihood, to incorporate polygenomic samples and simultaneously estimate allele frequency and COI. This approach was tested via simulations then applied to SNP data from cross-sectional surveys performed in three Ugandan sites with varying malaria transmission. We show that THE REAL McCOIL consistently outperforms COIL on simulated data, particularly when most infections are polygenomic. Using field data we show that, unlike with COIL, we can distinguish epidemiologically relevant differences in COI between and within these sites. Surprisingly, for example, we estimated high average COI in a peri-urban subregion with lower transmission intensity, suggesting that many of these cases were imported from surrounding regions with higher transmission intensity. THE REAL McCOIL therefore provides a robust tool for understanding the molecular epidemiology of malaria across transmission settings.

The Cu migration behavior in PVD-CdS/PVD-Cu(In,Ga)Se2 (CIGS) heterojunctions is investigated by high-resolution electron microscopy (HREM) and energy dispersive X-ray spectroscopy (EDS). Incorporation of Cu into the CdS forms Cu-rich domains but has no effect on epitaxy of the CdS. Epitaxy is commonly observed in the CdS studied. Secondary ion mass spectroscopy depth profiles confirm the presence of Cu in the CdS. In some cases, Cd is completely replaced by Cu, resulting in a Cu-S binary compound epitaxially grown on the CIGS and fully coherent with the surrounding CdS. This is most likely to be cubic Cu2S, based on lattice spacing measurements from HREM images and EDS elemental quantification. In addition, we find that the buffer layer crystal structure influences the extent of Ga depletion at the CIGS surface, which is more pronounced adjacent to zinc-blende CdS than wurtzite CdS. Density functional theory calculations reveal that Cu clustering and different Ga depletion widths can be attributed to the inherent anisotropy of wurtzite CdS and differences in CIGS point-defect migration barriers. Understanding the influence of these effects on device properties is a critical step in developing more efficient CdS/CIGS-based photovoltaics.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The POCUS Certification Academy, a subdivision of Inteleos, a non-profit certification organization, is striving to promote global standards and international certifications in the field of POCUS to enhance clinician proficiency and ensure patient safety. By offering relevant rigorous assessments, developing continuing education requirements, and promoting the use of point-of-care ultrasound worldwide, the POCUS Certification Academy is laying the foundation for the highest global standards in POCUS credentialing.

In January 2020, a novel betacoronavirus (family Coronaviridae), named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified as the etiological agent of a cluster of pneumonia cases occurring in Wuhan City, Hubei Province, China.sup.1,2. The disease arising from SARS-CoV-2 infection, coronavirus disease 2019 (COVID-19), subsequently spread rapidly causing a worldwide pandemic. Here we examine the added value of near real-time genome sequencing of SARS-CoV-2 in a subpopulation of infected patients during the first 10 weeks of COVID-19 containment in Australia and compare findings from genomic surveillance with predictions of a computational agent-based model (ABM). Using the Australian census data, the ABM generates over 24 million software agents representing the population of Australia, each with demographic attributes of an anonymous individual. It then simulates transmission of the disease over time, spreading from specific infection sources, using contact rates of individuals within different social contexts. We report that the prospective sequencing of SARS-CoV-2 clarified the probable source of infection in cases where epidemiological links could not be determined, significantly decreased the proportion of COVID-19 cases with contentious links, documented genomically similar cases associated with concurrent transmission in several institutions and identified previously unsuspected links. Only a quarter of sequenced cases appeared to be locally acquired and were concordant with predictions from the ABM. These high-resolution genomic data are crucial to track cases with locally acquired COVID-19 and for timely recognition of independent importations once border restrictions are lifted and trade and travel resume. The combination of nearly real-time genome sequencing of SARS-CoV-2 in infected patients during the first 10 weeks of COVID-19 containment in Australia and epidemiological modeling is helping in understanding the dynamics of the COVID-19 pandemic and potentially guiding public health decisions., Author(s): Rebecca J. Rockett [sup.1] [sup.2] , Alicia Arnott [sup.1] [sup.2] [sup.3] , Connie Lam [sup.1] [sup.2] , Rosemarie Sadsad [sup.1] [sup.2] [sup.4] , Verlaine Timms [sup.1] [sup.2] , Karen-Ann [...]

There is growing evidence that domain walls in ferroics can possess emergent properties that are absent in the bulk. For example, 180° ferroelectric domain walls in the ferroelectric-antiferromagnetic BiFeO3 are particularly interesting because they have been predicted to possess a range of intriguing behaviors, including electronic conduction and enhanced magnetization. To date, however, ordered arrays of such domain structures have not been reported. Here, we report the observation of 180° stripe nanodomains in (110)-oriented BiFeO3 thin films grown on orthorhombic GdScO3 (010)O substrates and their impact on exchange coupling to metallic ferromagnets. Nanoscale ferroelectric 180° stripe domains with {112̅} domain walls were observed in films

Background: The -α3.7I-thalassaemia deletion is very common throughout Africa because it protects against malaria. When undertaking studies to investigate human genetic adaptations to malaria or other diseases, it is important to account for any confounding effects of α-thalassaemia to rule out spurious associations. Methods: In this study, we have used direct α-thalassaemia genotyping to understand why GWAS data from a large malaria association study in Kilifi Kenya did not identify the α-thalassaemia signal. We then explored the potential use of a number of new approaches to using GWAS data for imputing α-thalassaemia as an alternative to direct genotyping by PCR. Results: We found very low linkage-disequilibrium of the directly typed data with the GWAS SNP markers around α-thalassaemia and across the haemoglobin-alpha (HBA) gene region, which along with a complex haplotype structure, could explain the lack of an association signal from the GWAS SNP data. Some indirect typing methods gave results that were in broad agreement with those derived from direct genotyping and could identify an association signal, but none were sufficiently accurate to allow correct interpretation compared with direct typing, leading to confusing or erroneous results. Conclusions: We conclude that going forwards, direct typing methods such as PCR will still be required to account for α-thalassaemia in GWAS studies.

Objectives: To describe local operational aspects of the coronavirus disease 2019 (COVID-19) response during the first three waves of outbreaks in New South Wales (NSW), Australia, which began in January, July and December 2020. Type of program or service: Public health outbreak response. Methods: Narrative with epidemiological linking and genomic testing. Results: Epidemiological linking and genomic testing found that during the first wave of COVID-19 in NSW, a large number of community transmissions went undetected because of limited testing for the virus and limited contact tracing of cases. The second wave of COVID-19 in NSW emerged following reintroduction from the second wave in Victoria, Australia in July 2020, and the third wave followed undetected introduction from overseas. By the second and third waves, cases could be more effectively detected and isolated through an increased ability to test and contact trace, and to rapidly genomic sequence severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) isolates, allowing most cases to be identified and epidemiologically linked. This greater certainty in understanding chains of transmission resulted in control of the outbreaks despite less stringent restrictions on the community, by using a refined strategy of targeted shutdown, restrictions on cases, their close contacts, identified hotspots and venues of concern rather than a whole of community lockdown. Risk assessments of potential transmission sites were constantly updated through our evolving experience with transmission events. However, this refined strategy did leave the potential for large point source outbreaks should any cases go undetected. [Addendum] A fourth wave that began in Sydney in June 2021 challenged this strategy due to the more transmissible nature of the Delta variant of SARS-CoV-2. Lessons learnt: A wave of COVID-19 infections can develop quickly from one infected person. The community needs to remain vigilant, adhering to physical distancing measures, signing in to venues they visit, and getting tested if they have any symptoms. Signing out of venues on exit allows public health resources to be used more efficiently to respond to outbreaks.

Introduction: Personas are based on real-life typologies of people that can be used to create characters and messages to communicate important health information through relatable narrative storylines. Persona development is data-driven and can involve multiple phases of formative research and evaluation; however, personas are largely underutilized in digital health research. The purpose of this study was to create and document persona development to deliver narrative-focused health education for parents on Twitter with the goal of increasing uptake of HPV vaccination among adolescents.Methods: Leveraging data from a mixed-method study conducted in the U.S. with a diverse population of parents with adolescents ages 9–14, we used both qualitative and quantitative data (e.g., the National Immunization Survey—Teen, focus groups, and social media) to create personas. These data sources were used to identify and develop key characteristics for personas to reflect a range of parents and their diverse understandings and experiences related to HPV vaccination. A parent advisory board provided insight and helped refine persona development.Results: Four personas emerged and were characterized as the (1) Informed Altruist, (2) Real Talker, (3) Information Gatherer, and (4) Supporter. Characteristics differed across personas and provided insights into targeted narrative strategies. Described attributes included demographics, psychographics, communication style, vaccine goals and aspirations, vaccine challenges and frustrations, and vaccine hesitancy.Discussion: This work demonstrates how multiple data sources can be used to create personas to deliver social media messages that can address the diverse preferences and needs of parents for HPV vaccine information. With increasing usage of social media for health information among parents, it is important for researchers to consider marketing and design thinking to create health communication messages that resonate with audiences.

Background: National Malaria Control Programmes (NMCPs) currently make limited use of parasite genetic data. We have developed GenRe-Mekong, a platform for genetic surveillance of malaria in the Greater Mekong Subregion (GMS) that enables NMCPs to implement large-scale surveillance projects by integrating simple sample collection procedures in routine public health procedures. Methods: Samples from symptomatic patients are processed by SpotMalaria, a high-throughput system that produces a comprehensive set of genotypes comprising several drug resistance markers, species markers and a genomic barcode. GenRe-Mekong delivers Genetic Report Cards, a compendium of genotypes and phenotype predictions used to map prevalence of resistance to multiple drugs. Results: GenRe-Mekong has worked with NMCPs and research projects in eight countries, processing 9623 samples from clinical cases. Monitoring resistance markers has been valuable for tracking the rapid spread of parasites resistant to the dihydroartemisinin-piperaquine combination therapy. In Vietnam and Laos, GenRe-Mekong data have provided novel knowledge about the spread of these resistant strains into previously unaffected provinces, informing decision-making by NMCPs. Conclusions: GenRe-Mekong provides detailed knowledge about drug resistance at a local level, and facilitates data sharing at a regional level, enabling cross-border resistance monitoring and providing the public health community with valuable insights. The project provides a rich open data resource to benefit the entire malaria community. Funding: The GenRe-Mekong project is funded by the Bill and Melinda Gates Foundation (OPP11188166, OPP1204268). Genotyping and sequencing were funded by the Wellcome Trust (098051, 206194, 203141, 090770, 204911, 106698/B/14/Z) and Medical Research Council (G0600718). A proportion of samples were collected with the support of the UK Department for International Development (201900, M006212), and Intramural Research Program of the National Institute of Allergy and Infectious Diseases.

In visual environments, selective attention must be employed to focus on task-relevant stimuli. A key question here concerns the extent to which other stimuli within the visual field influence target processing. In this study, we ask whether face identity matching is subject to similar effects from irrelevant stimuli in the visual field, specifically task-irrelevant people. Although most previous studies rely on highly controlled face and body stimuli presented in isolation, here we use a more realistic environment. Participants take the role of passport officers and must match a person's face to their photo-ID, while other people appear in the background, waiting to be processed. Presenting an interactive virtual environment on screen (Experiments 1 and 2) or in immersive VR (Experiment 3), we generally found no evidence for distraction from background people on face-matching accuracy. However, when immersed in VR, an angry crowd in the background delayed matching speed while not affecting accuracy. We discuss the theoretical implications of these results and their potential importance in practical settings. [ABSTRACT FROM AUTHOR]