Spatial Analysis of Drug-Susceptible and Multidrug-Resistant Cases of Tuberculosis, Ho Chi Minh City, Vietnam, 2020-2023.

We characterized the spatial distribution of drug-susceptible (DS) and multidrug-resistant (MDR) tuberculosis (TB) cases in Ho Chi Minh City, Vietnam, a major metropolis in southeastern Asia, and explored demographic and socioeconomic factors associated with local TB burden. Hot spots of DS and MDR TB incidence were observed in the central parts of Ho Chi Minh City, and substantial heterogeneity was observed across wards. Positive spatial autocorrelation was observed for both DS TB and MDR TB. Ward-level TB incidence was associated with HIV prevalence and the male proportion of the population. No ward-level demographic and socioeconomic indicators were associated with MDR TB case count relative to total TB case count. Our findings might inform spatially targeted TB control strategies and provide insights for generating hypotheses about the nature of the relationship between DS and MDR TB in Ho Chi Minh City and the wider southeastern region of Asia.

Imputation strategies for genomic prediction using nanopore sequencing.

BACKGROUND: Genomic prediction describes the use of SNP genotypes to predict complex traits and has been widely applied in humans and agricultural species. Genotyping-by-sequencing, a method which uses low-coverage sequence data paired with genotype imputation, is becoming an increasingly popular SNP genotyping method for genomic prediction. The development of Oxford Nanopore Technologies' (ONT) MinION sequencer has now made genotyping-by-sequencing portable and rapid. Here we evaluate the speed and accuracy of genomic predictions using low-coverage ONT sequence data in a population of cattle using four imputation approaches. We also investigate the effect of SNP reference panel size on imputation performance. RESULTS: SNP array genotypes and ONT sequence data for 62 beef heifers were used to calculate genomic estimated breeding values (GEBVs) from 641 k SNP for four traits. GEBV accuracy was much higher when genome-wide flanking SNP from sequence data were used to help impute the 641 k panel used for genomic predictions. Using the imputation package QUILT, correlations between ONT and low-density SNP array genomic breeding values were greater than 0.91 and up to 0.97 for sequencing coverages as low as 0.1 × using a reference panel of 48 million SNP. Imputation time was significantly reduced by decreasing the number of flanking sequence SNP used in imputation for all methods. When compared to high-density SNP arrays, genotyping accuracy and genomic breeding value correlations at 0.5 × coverage were also found to be higher than those imputed from low-density arrays. CONCLUSIONS: Here we demonstrated accurate genomic prediction is possible with ONT sequence data from sequencing coverages as low as 0.1 × , and imputation time can be as short as 10 min per sample. We also demonstrate that in this population, genotyping-by-sequencing at 0.1 × coverage can be more accurate than imputation from low-density SNP arrays.

Ontologies related to livestock for the Global Burden of Animal Diseases programme: a review.

The Global Burden of Animal Diseases (GBADs) programme aims to assess the impact of animal health on agricultural animals, livestock production systems and associated communities worldwide. As part of the objectives of GBADs'Animal Health Ontology theme, the programme reviewed conceptual frameworks, ontologies and classification systems in biomedical science. The focus was on data requirements in animal health and the connections between animal health and human and environmental health. In May 2023, the team conducted searches of recognised repositories of biomedical ontologies, including BioPortal, Open Biological and Biomedical Ontology Foundry, and Ontology Lookup Service, to identify animal and livestock ontologies and those containing relevant concepts. Sixteen ontologies were found, covering topics such as surveillance, anatomy and genetics. Notable examples include the Animal Trait Ontology for Livestock, the Animal Health Surveillance Ontology, the National Center for Biotechnology Information Taxonomy and the Uberon Multi-Species Anatomy Ontology. However, some ontologies lacked class definitions for a significant portion of their classes. The review highlights the need for domain evidence to support proposed models, critical appraisal of external ontologies before reuse, and external expert reviews along with statistical tests of agreements. The findings from this review informed the structural framework, concepts and rationales of the animal health ontology for GBADs. This animal health ontology aims to increase the interoperability and transparency of GBADs data, thereby enabling estimates of the impacts of animal diseases on agriculture, livestock production systems and associated communities globally.

Le programme " Impact mondial des maladies animales " (GBADs) vise à évaluer l'impact de la santé animale sur les animaux d'élevage, les systèmes de production animale et les communautés liées à ce secteur d'activités dans le monde. Afin de définir une ontologie de la santé animale répondant aux objectifs du GBADs, le programme a procédé à un examen des cadres conceptuels, des ontologies et des systèmes de classification actuellement appliqués en sciences biomédicales. Il s'agissait de définir les besoins en données dans le domaine de la santé animale ainsi que les connexions entre la santé animale, la santé publique et la santé environnementale. En mai 2023, l'équipe a procédé à des recherches dans des référentiels reconnus d'ontologies biomédicales, notamment BioPortal, Open Biological and Biomedical Ontology Foundry et Ontology Lookup Service, afin de recenser les ontologies relatives aux animaux et au bétail ainsi que celles contenant des concepts pertinents. Seize ontologies ont été relevées, couvrant des thèmes tels que la surveillance, l'anatomie et la génétique. Parmi les exemples notables on peut citer : Animal Trait Ontology for Livestock (ontologie dédiée aux caractères phénotypiques des animaux d'élevage), Animal Health Surveillance Ontology (ontologie dédiée à la surveillance de la santé animale), National Center for Biotechnology Information Taxonomy (la base de données Taxonomie du Centre américain pour les informations biotechnologiques), et Uberon Multi-Species Anatomy Ontology (ontologie anatomique représentant diverses espèces animales). Il a cependant été constaté que certaines ontologies ne disposent pas de définitions de classes pour une grande partie des classes qui les composent. L'examen a souligné l'importance d'étayer les modèles proposés par des données issues des spécialités en question, de procéder à une évaluation critique des ontologies externes avant de les réutiliser et de faire effectuer des examens complémentaires par des experts externes ainsi que des tests statistiques de concordance. Les résultats de cette étude ont apporté des éléments permettant de définir le cadre structurel, les concepts et les principes de l'ontologie relative à la santé animale destinée au GBADs. Cette ontologie de la santé animale vise à accroître l'interopérabilité et la transparence des données du GBADs, ce qui permet d'effectuer des estimations de l'impact des maladies animales sur l'agriculture, les systèmes de production animale et les communautés associées à ce secteur d'activités à l'échelle mondiale.

El programa sobre el impacto global de las enfermedades animales (GBADs) tiene como objetivo evaluar el impacto de la sanidad animal en los animales de granja, los sistemas de producción ganadera y las comunidades conexas en todo el mundo. Como parte de los objetivos en torno al tema de la ontología de la sanidad animal del GBADs, el programa revisó marcos conceptuales, ontologías y sistemas de clasificación en el ámbito de la ciencia biomédica. Se hizo hincapié en los requisitos de datos sobre la sanidad animal y en las conexiones entre la sanidad animal y la salud humana y ambiental. En mayo de 2023, el equipo realizó búsquedas en repositorios reconocidos de ontologías biomédicas, como BioPortal, Open Biological and Biomedical Ontology Foundry y Ontology Lookup Service, para identificar no solo ontologías animales y ganaderas, sino también aquellas que incluyeran conceptos relevantes. En este sentido, se encontraron dieciséis ontologías, que abarcan temas como vigilancia, anatomía y genética. Entre los ejemplos más destacados figuran Animal Trait Ontology for Livestock (Ontología de Características Animales para el Ganado), Animal Health Surveillance Ontology (Ontología de Vigilancia de la Sanidad Animal), National Center for Biotechnology Information Taxonomy (la base de datos Taxonomía del Centro Nacional para la Información Biotecnológica) y Uberon Multi-Species Anatomy Ontology (Ontología Anatómica de Especies Múltiples). Sin embargo, algunas ontologías carecían de definiciones para una parte significativa de sus clases. La revisión pone de relieve la necesidad de contar con datos probatorios del ámbito en cuestión que respalden los modelos propuestos, una evaluación crítica de las ontologías externas antes de su reutilización y revisiones de expertos externos junto con pruebas estadísticas de los acuerdos. Los resultados de esta revisión han servido de base para el marco estructural, los conceptos y los fundamentos de la ontología de la sanidad animal para el GBADs. Esta ontología pretende aumentar la interoperabilidad y la transparencia de los datos del GBADs, permitiendo así estimar el impacto de las enfermedades animales en la agricultura, los sistemas de producción ganadera y las comunidades conexas en todo el mundo.

Global Burden of Animal Diseases informatics strategy, data quality and model interoperability.

The estimation of the global burden of animal diseases requires the integration of multidisciplinary models: economic, statistical, mathematical and conceptual. The output of one model often serves as input for another; therefore, consistency of the model components is critical. The Global Burden of Animal Diseases (GBADs) Informatics team aims to strengthen the scientific foundations of modelling by creating tools that address challenges related to reproducibility, as well as model, data and metadata interoperability. Aligning with these aims, several tools are under development: a) GBADs'Trusted Animal Information Portal (TAIL) is a data acquisition platform that enhances the discoverability of data and literature and improves the user experience of acquiring data. TAIL leverages advanced semantic enrichment techniques (natural language processing and ontologies) and graph databases to provide users with a comprehensive repository of livestock data and literature resources. b) The interoperability of GBADs'models is being improved through the development of an R-based modelling package and standardisation of parameter formats. This initiative aims to foster reproducibility, facilitate data sharing and enable seamless collaboration among stakeholders. c) The GBADs Knowledge Engine is being built to foster an inclusive and dynamic user community by offering data in multiple formats and providing user-friendly mechanisms to garner feedback from the community. These initiatives are critical in addressing complex challenges in animal health and underscore the importance of combining scientific rigour with user-friendly interfaces to empower global efforts in safeguarding animal populations and public health.

L'estimation de l'impact mondial des maladies animales nécessite l'utilisation intégrée de modèles issus de diverses disciplines : économiques, statistiques, mathématiques et conceptuels. Les données de sortie d'un modèle constituent souvent celles d'entrée d'un autre modèle ; la cohérence des composantes des différents modèles est donc primordiale. L'équipe informatique du programme " Impact mondial des maladies animales " (GBADs) s'efforce de consolider les bases scientifiques de l'utilisation des modèles en mettant au point des outils permettant de résoudre les problèmes de reproductibilité et d'améliorer l'interopérabilité entre les différents modèles, données et métadonnées. En phase avec ces objectifs, plusieurs outils sont en cours de développement : a) le Portail du GBADs " Trusted Animal Information Portal " (TAIL) est une plateforme d'acquisition de données qui facilite l'accès aux données et à la littérature, tout en améliorant l'expérience utilisateur lors de l'acquisition des données. Le portail TAIL s'appuie sur des techniques avancées d'enrichissement sémantique (traitement du langage naturel et ontologies) et sur des bases de données graphiques pour apporter aux utilisateurs un référentiel complet des données et des ressources documentaires relatives aux animaux d'élevage ; b) l'interopérabilité des modèles du GBADs est en voie d'amélioration grâce à la mise au point d'un progiciel de modélisation fondé sur R et à la normalisation des formats de paramètres. Cette initiative vise à favoriser la reproductibilité, à faciliter le partage de données et à permettre une collaboration transparente entre les parties prenantes ; c) le moteur de connaissances du GBADs, en cours de construction, vise à encourager une communauté d'utilisateurs inclusive et dynamique en proposant des données dans une multiplicité de formats ainsi que des mécanismes conviviaux pour recueillir les commentaires de la communauté. Ces initiatives se révéleront indispensables pour relever les défis complexes de la santé animale et soulignent l'importance d'associer une grande rigueur scientifique à la convivialité des interfaces, afin de donner encore plus d'élan aux efforts déployés dans le monde pour protéger les populations animales et la santé publique.

La estimación del impacto global de las enfermedades animales requiere la integración de modelos multidisciplinarios: económicos, estadísticos, matemáticos y conceptuales. El resultado de un modelo a menudo sirve de entrada para otro; por lo tanto, la coherencia entre los distintos componentes es fundamental. El equipo de informática del programa sobre el Impacto Global de las Enfermedades Animales (GBADs) tiene como objetivo fortalecer los fundamentos científicos de la modelización mediante la creación de herramientas que aborden los retos relacionados con la reproducibilidad, así como con la interoperabilidad de los modelos, datos y metadatos. En consonancia con estos objetivos, se están desarrollando varias herramientas: a) El Portal del GBADs "Trusted Animal Information Portal" (TAIL) es una plataforma de adquisición de datos que mejora tanto la descubribilidad de datos y bibliografía como la experiencia del usuario a la hora de obtener datos. El portal TAIL utiliza técnicas avanzadas de enriquecimiento semántico (procesamiento del lenguaje natural y ontologías), así como bases de datos de grafos, para ofrecer a los usuarios un repositorio completo de datos sobre ganadería y recursos bibliográficos. b) Se está mejorando la interoperabilidad de los modelos del GBADs mediante el desarrollo de un paquete de modelización en R y la normalización de los formatos de los parámetros. Esta iniciativa pretende fomentar la reproducibilidad, facilitar el intercambio de datos y permitir una colaboración fluida entre las partes interesadas. c) El Motor de Conocimiento del GBADs se está construyendo con el objetivo de fomentar una comunidad de usuarios inclusiva y dinámica, ofreciendo datos en diferentes formatos y proporcionando mecanismos fáciles de usar para recopilar comentarios de la comunidad. Estas iniciativas son fundamentales para hacer frente a los complejos retos en el ámbito de la sanidad animal y subrayan la importancia de combinar el rigor científico con interfaces fáciles de usar para potenciar los esfuerzos mundiales encaminados a proteger a las poblaciones animales y la salud pública.

Planning the future of oral health care workforce: Moving beyond demographic change.

The adoption of Universal Health Coverage for oral health care will not be sufficient to ensure that health care resources are accessible in accordance with needs for care. Government intervention in planning and allocating resources will be required to replace traditional market forces if market failure is not to be replaced by government failure. In this paper we explore the limitations of current 'fixed in time' approaches to planning the oral health care workforce and present an enhanced dynamic model for workforce planning that responds directly to changes in population, evidence-based best practice and new models of care.

Adsorption and Molecular Display of a Redox-Active Protein on Gold Nanoparticle Surfaces.

Engineered gold nanoparticles (AuNPs) have great potential in many applications due to their tunable optical properties, facile synthesis, and surface functionalization via thiol chemistry. When exposed to a biological environment, NPs are coated with a protein corona that can alter the NPs' biological identity but can also affect the proteins' structures and functions. Protein disulfide isomerase (PDI) is an abundant protein responsible for the disulfide formation and isomerization that contribute to overall cell redox homeostasis and signaling. Given that AuNPs are widely employed in nanomedicine and PDI plays a functional role in various diseases, the interactions between oxidized (oPDI) and reduced (rPDI) with 50 nm citrate-coated AuNPs (AuNPs) are examined in this study using various techniques. Upon incubation, PDI adsorbs to the AuNP surface, which leads to a reduction in its enzymatic activity despite limited changes in secondary structures. Partial enzymatic digestion followed by mass spectrometry analysis shows that orientation of PDI on the NP surface is dependent on both its oxidation state and the PDI:AuNP incubation ratios.

Periodontitis-resistant and -susceptible matriline regulation of gingival transcriptome in nonhuman primates.

OBJECTIVE: This report identified if gingival gene expression transcriptomes demonstrated unique profiles that discriminated periodontitis-susceptible (PDS) and periodontitis-resistant (PDR) animals in health and disease. BACKGROUND: Nonhuman primates generally organize their social groups based upon matriline origin. We have used a multi-generational colony of rhesus macaques to identify matrilines presenting with significant differences in periodontitis (e.g., earlier age onset, greater prevalence, and severity). METHODS: Animals from 12 to 23 years of age (n = 17; 8 - PDR, 9 - PDS) were entered into a ligature-induced periodontitis trial. Gingival biopsies were taken at baseline and 0.5, 1, 3, and 5 months post-ligation, and microarray analysis was used to quantify gene expression in samples at each time point. RESULTS: Over 1000 genes showed significant (p < .01) differences in the PDR versus PDS animals at baseline. The frequency of differences generally decreased during the disease process, and increased with resolution (i.e., 5 months). A nearly 2:1 ratio of elevated gene levels was noted in baseline PDR samples that included up-regulated MMPs, Fc receptors, chemokines, interleukins, and innate immune receptors, and down-regulated genes particularly related to epithelial biology. Most dramatically, there was a skewed differential expression of adaptive immune response genes in the PDR and epithelial cell structure/function genes in PDS samples. CONCLUSIONS: The results demonstrate substantive differences in gingival tissue response capacity/programming in PDR and PDS samples that may contribute to the differences in clinical outcomes related to the heritability of disease risk through matrilines.

Macrophage-related gingival transcriptomic patterns and microbiome alterations in experimental periodontitis in nonhuman primates.

OBJECTIVE: This study examined the microbiome features specifically related to host macrophage polarization in health, initiation and progression of periodontitis, and in resolution samples using a nonhuman primate model of ligature-induced periodontitis. BACKGROUND: The oral microbiome is a complex of bacterial phyla, genera, and species acquired early in life into the individual autochthonous oral ecology. The microbiome changes overtime in response to both intrinsic and extrinsic stressors, and transitions to a dysbiotic ecology at sites of periodontal lesions. METHODS: Comparisons were made between the microbial and host features in young (≤7 years) and adult (≥12 years) cohorts of animals. Footprints of macrophage-related genes in the gingival tissues were evaluated using expression profiles including M0, M1, and M2 related genes. RESULTS: Within the gingival tissues, similar macrophage-related gene patterns were observed with significant increases with disease initiation and continued elevation throughout disease in both age groups. Approximately, 70% of the taxa were similar in relative abundance between the two groups; however, the adults showed a large number of OTUs that were significantly altered compared with the younger animals. Developing a correlation map identified three major node levels of interactions that comprised approximately ⅓ of the Operational Taxonomic Units (OTUs) that dominated the microbiomes across the samples. Also noted was a much greater frequency of significant correlations of individual OTUs with the macrophage phenotype markers, compared with disease and resolution samples in both age groups, with a greater frequency in the younger group. Moreover, these correlations were assigned to differentially expressed genes representing M0, M1, and M2-related phenotypes. A cluster analyses across the macrophage-related transcriptome and the OTUs demonstrated multiple somewhat distinct bacterial consortia, incorporating both commensal and putative pathogens, linked to the gene responses that differed in health, disease, and resolution samples. Finally, there were minimal alterations in the OTUs in individual clusters with specific macrophage-related responses in the younger group, while in the adult samples substantial variations were noted with genes from all macrophage phenotypes. CONCLUSIONS: The results confirmed important features that could reflect macrophage polarization in periodontal lesions, and provided some initial data supporting specific members of the oral microbiome feature prominently related to specific gene response patterns consistent with macrophages in the gingival tissues.

Isolation Methods Influence the Protein Corona Composition on Gold-Coated Iron Oxide Nanoparticles.

Upon exposure to a biological environment, nanoparticles (NPs) acquire biomolecular coatings, the most studied of which is the protein corona. This protein corona gives NPs a new biological identity that will determine various biological responses including cellular uptake, biodistribution, and toxicity. The standard method to isolate NPs from a biological matrix in order to study their coronas is centrifugation, but more gentle means of retrieval may enable deeper understanding of both irreversibly bound hard coronas and more loosely bound soft coronas. In this study, magnetic gold-coated iron oxide NPs were incubated with rainbow trout gill cell total protein extracts and mass spectrometric proteomic analysis was conducted to determine the composition of the protein coronas isolated by either centrifugation or magnetic retrieval. The number of washes were varied to strip away the soft coronas and isolate the hard corona. Hundreds of proteins were adsorbed to the NPs. Some proteins were common to all isolation methods and many others were particular to the isolation method. Some qualitative trends in protein character were discerned from quantitative proteomic analyses, but more importantly, a new kind of protein corona was identified, mixed corona, in which the labile or inert nature of the protein-NP interaction is dependent upon sample history.

[A catamenial pneumothorax, an unknown entity]. / Le pneumothorax cataménial, une entité méconnue.

A 31-year-old patient is admitted to the emergency room because of an acute right thoracic pain associated with a dyspnea. The patient reports the stopping of Decapeptyl®, a treatment taken in regards to an endometriosis, but interrupted to get pregnant. An x-ray highlights a pneumothorax of 15 mm at the right apical level. It is a second episode for this patient. Catamenial pneumothorax is one of the most frequent manifestation in terms of a thoracic endometriosis syndrome (TES). It concerns a rare pathology, unrecognized and underdiagnosed. The diagnosis should be invoked on all patients having the childbearing age who are presenting themselves at the emergencies with a right thoracic pain. The medical care is multidisciplinary, the association of a hormonal therapy and then a surgical treatment being the best therapeutical approach. This case report describes the recurrence of a catamenial pneumotorax induced by the stopping of the endometriosis treatment and reviews the physiopathology, the diagnosis and its multidisciplinary management.

Une patiente de 31 ans est admise aux urgences pour douleur thoracique droite apparue brutalement et associée à une dyspnée. La patiente rapporte l'arrêt du Decapeptyl®, traitement pris dans le cadre d'une endométriose, mais interrompu pour un désir de grossesse. Une radiographie mettra en évidence un pneumothorax de 15 mm au niveau apical droit. Il s'agit du deuxième épisode chez cette patiente. Le pneumothorax cataménial (PC) est l'une des manifestations les plus fréquentes dans le cadre d'un syndrome d'endométriose thoracique (SET). Il s'agit d'une pathologie rare, méconnue et sous-diagnostiquée. Il est à évoquer chez toutes patientes en âge de procréer se présentant aux urgences avec une douleur thoracique droite. La prise en charge est multidisciplinaire, l'association d'un traitement hormonal, puis chirurgical, semble être la meilleure approche thérapeutique. Cet article rapporte la récidive d'un PC, récidive induite par l'arrêt du traitement de l'endométriose, et revoit la physiopathologie, le diagnostic et la prise en charge de celui-ci.

Keratinocytes: innate immune cells in atopic dermatitis.

The skin is a unique immune organ that constitutes a complex network of physical, chemical and microbiological barriers against external insults. Keratinocytes are the most abundant cell type in the epidermis. These cells form the physical skin barrier and represent the first line of the host defense system by sensing pathogens via innate immune receptors, initiating anti-microbial responses and producing various cytokines, chemokines and anti-microbial peptides, which are important events in immunity. A damaged epidermal barrier in atopic dermatitis allows the penetration of potential allergens and pathogens to activate keratinocytes. Among the dysregulation of immune responses in atopic dermatitis, activated keratinocytes play a role in several biological processes that contribute to the pathogenesis of atopic dermatitis. In this review, we summarize the current understanding of the innate immune functions of keratinocytes in the pathogenesis of atopic dermatitis, with a special emphasis on skin-derived anti-microbial peptides and atopic dermatitis-related cytokines and chemokines in keratinocytes. An improved understanding of the innate immunity mediated by keratinocytes can provide helpful insight into the pathophysiological processes of atopic dermatitis and support new therapeutic efforts.

Investigation of alkali and alkaline earth solvation structures in tetraglyme solvent.

This study compares molecular calculations performed with molecular and periodic codes through an investigation of the solvation structures of alkali and alkaline earth metal ions in tetraglyme solution. The two codes are able to produce equivalent structural and energetic information at the same level of theory, and in the presence of the implicit solvation model or not. This comparison reveals that molecular optimisations can be performed with periodic codes and used directly as input models for interface or electrochemistry calculations in order to preserve the solvent-solute interaction and the cavitation energy. By a rigorous comparison, we have demonstrated that equivalent energetic values can be obtained with the conventional PBE-D3 and the newly developed SCAN-rVV10 functionals. Nevertheless, as far as the vibrational features are concerned and when the molecule possesses a highly conjugated system, the SCAN-rVV10 functional is required to describe the vibrational modes properly. The computed IR/Raman spectra can thus be used as essential information to determine the first solvation shell of metal ions in glyme-based solutions. In tetraglyme solution, the alkali and alkaline earth metal ions exhibit a diverse solvation structure. Small ions like Li+ and Mg2+ tend to adopt a coordination number of five or six, while larger ions, Na+, K+, and Ca2+, prefer an eight-coordinated environment, and the metal-ligand interaction increases in the order K+-O < Na+-O < Li+-O < Ca2+-O < Mg2+-O. The solvation spheres play a significant role in the stability and the reactivity of the solvated ions, and can thus be used as input models to construct the solvation structure in more sophisticated electrolytes, such as polyethylene oxide, or perform electrochemical calculations.

Aerosolisation during tracheal intubation and extubation in an operating theatre setting.

Aerosol-generating procedures such as tracheal intubation and extubation pose a potential risk to healthcare workers because of the possibility of airborne transmission of infection. Detailed characterisation of aerosol quantities, particle size and generating activities has been undertaken in a number of simulations but not in actual clinical practice. The aim of this study was to determine whether the processes of facemask ventilation, tracheal intubation and extubation generate aerosols in clinical practice, and to characterise any aerosols produced. In this observational study, patients scheduled to undergo elective endonasal pituitary surgery without symptoms of COVID-19 were recruited. Airway management including tracheal intubation and extubation was performed in a standard positive pressure operating room with aerosols detected using laser-based particle image velocimetry to detect larger particles, and spectrometry with continuous air sampling to detect smaller particles. A total of 482,960 data points were assessed for complete procedures in three patients. Facemask ventilation, tracheal tube insertion and cuff inflation generated small particles 30-300 times above background noise that remained suspended in airflows and spread from the patient's facial region throughout the confines of the operating theatre. Safe clinical practice of these procedures should reflect these particle profiles. This adds to data that inform decisions regarding the appropriate precautions to take in a real-world setting.

A Trial of Itraconazole or Amphotericin B for HIV-Associated Talaromycosis.

BACKGROUND: Talaromyces marneffei infection is a major cause of human immunodeficiency virus (HIV)-related death in South and Southeast Asia. Guidelines recommend initial treatment with amphotericin B deoxycholate, but this drug has substantial side effects, a high cost, and limited availability. Itraconazole is available in oral form, is associated with fewer unacceptable side effects than amphotericin, and is widely used in place of amphotericin; however, clinical trials comparing these two treatments are lacking. METHODS: In this open-label, noninferiority trial, we randomly assigned 440 HIV-infected adults who had talaromycosis, confirmed by either microscopy or culture, to receive either intravenous amphotericin B deoxycholate (amphotericin) (219 patients), at a dose of 0.7 to 1.0 mg per kilogram of body weight per day, or itraconazole capsules (221 patients), at a dose of 600 mg per day for 3 days, followed by 400 mg per day, for 11 days; thereafter, all the patients received maintenance therapy with itraconazole. The primary outcome was all-cause mortality at week 2. Secondary outcomes included all-cause mortality at week 24, the time to clinical resolution of talaromycosis, early fungicidal activity, relapse of talaromycosis, development of the immune reconstitution inflammatory syndrome (IRIS), and the side-effect profile. RESULTS: The risk of death at week 2 was 6.5% in the amphotericin group and 7.4% in the itraconazole group (absolute risk difference, 0.9 percentage points; 95% confidence interval [CI], -3.9 to 5.6; P<0.001 for noninferiority); however, the risk of death at week 24 was 11.3% in the amphotericin group and 21.0% in the itraconazole group (absolute risk difference, 9.7 percentage points; 95% CI, 2.8 to 16.6; P=0.006). Treatment with amphotericin was associated with significantly faster clinical resolution and fungal clearance and significantly lower rates of relapse and IRIS than itraconazole. The patients who received amphotericin had significantly higher rates of infusion-related reactions, renal failure, hypokalemia, hypomagnesemia, and anemia than patients in the itraconazole group. CONCLUSIONS: Amphotericin was superior to itraconazole as initial treatment for talaromycosis with respect to 6-month mortality, clinical response, and fungicidal activity. (Funded by the Medical Research Council and others; IVAP Current Controlled Trials number, ISRCTN59144167 .).

Virus-Sized Gold Nanorods: Plasmonic Particles for Biology.

Plasmons, collective oscillations of conduction-band electrons in nanoscale metals, are well-known phenomena in colloidal gold and silver nanocrystals that produce brilliant visible colors in these materials that depend on the nanocrystal size and shape. Under illumination at or near the plasmon bands, gold and silver nanocrystals exhibit properties that enable fascinating biological applications: (i) the nanocrystals elastically scatter light, providing a straightforward way to image them in complex aqueous environments; (ii) the nanocrystals produce local electric fields that enable various surface-enhanced spectroscopies for sensing, molecular diagnostics, and boosting of bound fluorophore performance; (iii) the nanocrystals produce heat, which can lead to chemical transformations at or near the nanocrystal surface and can photothermally destroy nearby cells. While all the above-mentioned applications have already been well-demonstrated in the literature, this Account focuses on several other aspects of these nanomaterials, in particular gold nanorods that are approximately the size of viruses (diameters of ∼10 nm, lengths up to 100 nm). Absolute extinction, scattering, and absorption properties are compared for gold nanorods of various absolute dimensions, and references for how to synthesize gold nanorods with four different absolute dimensions are provided. Surface chemistry strategies for coating nanocrystals with smooth or rough shells are detailed; specific examples include mesoporous silica and metal-organic framework shells for porous (rough) coatings and polyelectrolyte layer-by-layer wrapping for "smooth" shells. For self-assembled-monolayer molecular coating ligands, the smoothest shells of all, a wide range of ligand densities have been reported from many experiments, yielding values from less than 1 to nearly 10 molecules/nm2 depending on the nanocrystal size and the nature of the ligand. Systematic studies of ligand density for one particular ligand with a bulky headgroup are highlighted, showing that the highest ligand density occurs for the smallest nanocrystals, even though these ligand headgroups are the most mobile as judged by NMR relaxation studies. Biomolecular coronas form around spherical and rod-shaped nanocrystals upon immersion into biological fluids; these proteins and lipids can be quantified, and their degree of adsorption depends on the nanocrystal surface chemistry as well as the biophysical characteristics of the adsorbing biomolecule. Photothermal adsorption and desorption of proteins on nanocrystals depend on the enthalpy of protein-nanocrystal surface interactions, leading to light-triggered alteration in protein concentrations near the nanocrystals. At the cellular scale, gold nanocrystals exert genetic changes at the mRNA level, with a variety of likely mechanisms that include alteration of local biomolecular concentration gradients, changes in mechanical properties of the extracellular matrix, and physical interruption of key cellular processes-even without plasmonic effects. Microbiomes, both organismal and environmental, are the likely first point of contact of nanomaterials with natural living systems; we see a major scientific frontier in understanding, predicting, and controlling microbe-nanocrystal interactions, which may be augmented by plasmonic effects.

Experimental Demonstration of Hadron Beam Cooling Using Radio-Frequency Accelerated Electron Bunches.

Cooling of beams of gold ions using electron bunches accelerated with radio-frequency systems was recently experimentally demonstrated in the Relativistic Heavy Ion Collider at Brookhaven National Laboratory. Such an approach is new and opens the possibility of using this technique at higher energies than possible with electrostatic acceleration of electron beams. The challenges of this approach include generation of electron beams suitable for cooling, delivery of electron bunches of the required quality to the cooling sections without degradation of beam angular divergence and energy spread, achieving the required small angles between electron and ion trajectories in the cooling sections, precise velocity matching between the two beams, high-current operation of the electron accelerator, as well as several physics effects related to bunched-beam cooling. Here we report on the first demonstration of cooling hadron beams using this new approach.

Cervical pessary vs vaginal progesterone for prevention of preterm birth in women with twin pregnancy and short cervix: economic analysis following randomized controlled trial.

OBJECTIVE: To compare the cost-effectiveness of cervical pessary vs vaginal progesterone to prevent preterm birth and neonatal morbidity in women with twin pregnancy and a short cervix. METHODS: Between 4 March 2016 and 3 June 2017, we performed this economic analysis following a randomized controlled trial (RCT), performed at My Duc Hospital, Ho Chi Minh City, Vietnam, that compared cervical pessary to vaginal progesterone in women with twin pregnancy and cervical length < 38 mm between 16 and 22 weeks of gestation. We used morbidity-free neonatal survival as a measure of effectiveness. Data on pregnancy outcome, maternal morbidity and neonatal complications were collected prospectively from medical files; additional information was obtained via telephone interviews with the patients. The incremental cost-effectiveness ratio was calculated as the incremental cost required to achieve one extra surviving morbidity-free neonate in the pessary group compared with in the progesterone group. Probabilistic and one-way sensitivity analyses were also performed. RESULTS: During the study period, we screened 1113 women with twin pregnancy, of whom 300 fulfilled the inclusion criteria of the RCT and gave informed consent to participate. These women were assigned randomly to receive cervical pessary (n = 150) or vaginal progesterone (n = 150), with two women and one woman, respectively, being lost to follow-up. The rate of morbidity-free neonatal survival was significantly higher in the pessary group compared with the progesterone group (n = 241/296 (81.4%) vs 219/298 (73.5%); relative risk, 1.11 (95% CI, 1.02-1.21), P = 0.02). The mean total cost per woman was 3146 € in the pessary group vs 3570 € in the progesterone group (absolute difference, -424 € (95% CI, -842 to -3 €), P = 0.048). The cost per morbidity-free neonate was significantly lower in the pessary group compared with that in the progesterone group (2492 vs 2639 €; absolute difference, -147 € (95% CI, -284 to 10 €), P = 0.035). CONCLUSION: In women with twin pregnancy and a short cervix, cervical pessary improves significantly the rate of morbidity-free neonatal survival while reducing costs, as compared with vaginal progesterone. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Do Intracerebral Cytokine Responses Explain the Harmful Effects of Dexamethasone in Human Immunodeficiency Virus-associated Cryptococcal Meningitis?

BACKGROUND: The CryptoDex trial showed that dexamethasone caused poorer clinical outcomes and slowed fungal clearance in human immunodeficiency virus-associated cryptococcal meningitis. We analyzed cerebrospinal fluid (CSF) cytokine concentrations from participants over the first week of treatment to investigate mechanisms of harm and test 2 hypotheses: (1) dexamethasone reduced proinflammatory cytokine concentrations, leading to poorer outcomes and (2) leukotriene A4 hydrolase (LTA4H) genotype influenced the clinical impact of dexamethasone, as observed in tuberculous meningitis. METHODS: We included participants from Vietnam, Thailand, and Uganda. Using the Luminex system, we measured CSF concentrations of the following: interferon γ, tumor necrosis factor (TNF) α, granulocyte-macrophage colony-stimulating factor, monocyte chemoattractant 1, macrophage inflammatory protein 1α, and interleukin 6, 12p70, 8, 4, 10, and 17. We determined the LTA4H genotype based on the promoter region single-nucleotide polymorphism rs17525495. We assessed the impact of dexamethasone on cytokine concentration dynamics and the association between cytokine concentration dynamics and fungal clearance with mixed effect models. We measured the influence of LTA4H genotype on outcomes with Cox regression models. RESULTS: Dexamethasone increased the rate TNF-α concentration's decline in (-0.13 log2pg/mL/d (95% confidence interval, -.22 to -.06 log2pg/mL/d; P = .03), which was associated with slower fungal clearance (correlation, -0.62; 95% confidence interval, -.83 to -.26). LTA4H genotype had no statistically significant impact on outcome or response to dexamethasone therapy. Better clinical outcomes were associated with higher baseline concentrations of interferon γ. CONCLUSIONS: Dexamethasone may slow fungal clearance and worsen outcomes by increasing TNF-α concentration's rate of decline.

Evaluation of the Efficacy of Commercial Disinfectants Against Fusarium oxysporum f. sp. cubense Race 1 and Tropical Race 4 Propagules.

Panama disease caused by Fusarium oxysporum f. sp. cubense has devastated banana production worldwide. This work aimed to determine effective disinfectants against two races of F. oxysporum f. sp. cubense, race 1 and tropical race 4 (TR4), for implementation with on-farm biosecurity procedures against this disease following the outbreak of TR4 in North Queensland in 2015. A total of 32 commercial disinfectants were screened and their activity was assessed after ≤30 s, 5 min, 30 min, and 24 h of contact with an F. oxysporum f. sp. cubense suspension containing 105 chlamydospores/ml without and with soil added (0.05 g/ml). Of the disinfectants tested, the quaternary ammonium compounds containing ≥10% active ingredient were found to be the most effective against both F. oxysporum f. sp. cubense races. These products, when used at a 1:100 dilution, completely inhibited the survival of all F. oxysporum f. sp. cubense propagules across all the contact times regardless of the absence or presence of soil. The bioflavonoid product EvoTech 213 and bleach (10% sodium hypochlorite) used at a 1:10 dilution also eliminated all F. oxysporum f. sp. cubense propagules across all the contact times. None of the detergent-based or miscellaneous products tested were completely effective against both F. oxysporum f. sp. cubense races even used at a 1:10 dilution. Soil decreases the efficacy of disinfectants and therefore must be removed from contaminated items before treatments are applied.