Evaluation of critical parameters in the hollow-fibre system for tuberculosis: A case study of moxifloxacin

AimsThe hollow‐fibre system for tuberculosis (HFS‐TB) is a preclinical model qualified by the European Medicines Agency to underpin the anti‐TB drug development process. It can mimic in vivo pharmacokinetic (PK)–pharmacodynamic (PD) attributes of selected antimicrobials, which could feed into in silico models to inform the design of clinical trials. However, historical data and published protocols are insufficient and omit key information to allow experiments to be reproducible. Therefore, in this work, we aim to optimize and standardize various HFS‐TB operational procedures.MethodsFirst, we characterized bacterial growth dynamics with different types of hollow‐fibre cartridges, Mycobacterium tuberculosis strains and media. Second, we mimicked a moxifloxacin PK profile within hollow‐fibre cartridges, in order to check drug–fibres compatibility. Lastly, we mimicked the moxifloxacin total plasma PK profile in human after once daily oral dose of 400 mg to assess PK–PD after different sampling methods, strains, cartridge size and bacterial adaptation periods before drug infusion into the system.ResultsWe found that final bacterial load inside the HFS‐TB was contingent on the studied variables. Besides, we demonstrated that drug–fibres compatibility tests are critical preliminary HFS‐TB assays, which need to be properly reported. Lastly, we uncovered that the sampling method and bacterial adaptation period before drug infusion significantly impact actual experimental conclusions.ConclusionOur data contribute to the necessary standardization of HFS‐TB experiments, draw attention to multiple aspects of this preclinical model that should be considered when reporting novel results and warn about critical parameters in the HFS‐TB currently overlooked

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Barn i rörelse : Hur prioriteras rörelse på förskolan

Vårt syfte och intresse var att undersöka hur rörelse prioriteras inomhus på några olika förskolor i vår kommun. För att avgränsa vårt arbete har vi fokuserat oss på rörelse i lekhallen.Vi har genom ostrukturerade observationer och kvalitativa intervjuer med både pedagoger och barn på tre olika förskolor tagit reda på om rörelse prioriteras inomhus och i så fall hur? Resultatet visar utifrån frågeställningar, observationer och intervjuer med både pedagoger och barn att rörelse prioriteras utomhus. Förskolans lekhallar inbjuder till rörelse men rörelseytan är begräsad, lekhallen används både som matsal och för mer stillasittande lekar. Överlag uppmuntras barn inte till rörelse inomhus.I första hand är avsikten med vårt arbete att vi som blivande förskollärare ska inse och förstå vikten av barns behov av rörelse och hur den behöver prioriteras. I andra hand är vår önskan att vårt arbete ska väcka nya tankar hos fler pedagoger om rörelsens betydelse så det kommer till barnens fördel

Introduction to preschool : strategies for managing the gap between home and preschool

The overall aim of this article is to investigate Swedish preschool teachers’ perceptions of the interaction between home and institution in relation to children’s introduction to preschool. The focus of this article is on their talk about how they manage the gap between home and preschool in the introduction process. A discourse analysis is carried out, based on focus group interviews with seven preschool teacher teams that have started to use a more parent-active approach during the introduction of children to preschool. The results show that a parent-active introduction positions and governs parents to take a more self-regulative role in preschool from the beginning. The construction of the parent-active introduction discourse/practice produces new subject positions for the parents (and teachers) and creates expectations of intensified parental involvement in this institutional practice. Furthermore, the results indicate that the parents’ active introduction also changes the teachers’ own role and their attitudes toward the parents. The boundary work between the home and preschool seems to consist of negotiations and of the construction of an intermediate domain between home and preschool that draws on discourses of responsibility, performativity and efficiency

Utvecklingssamtal som uppgift och verktyg i förskollärares professionssträvanden i interaktion med föräldrar

Collaboration and communication between teachers and parents have during the last decades become increasingly highlighted in the Swedish preschool context. The aim of this study is to study the parent-teacher conference in the Swedish preschool and, based on interviews with preschool teachers, generate knowledge about how they view and the importance they give the parent-teacher conference as a social practice in the preschool and as a part of their profession. The analyses of the interviews show that the parent-teacher conference is an important tool for the teachers in order to create a professional relationship with the parents and to give them support in their parental role. Furthermore, the results show that the parent-teacher conference is central for creating a complete picture of the child, and that it can be seen as an   assessment practice for not only the child, the parents and the preschool as an institution but also for the preschool teachers themselves in their role as professionals

Förskoleföräldrars tankar om utvecklingssamtal

Hur upplever föräldrar utvecklingssamtal i förskolan? I denna artikel presenteras några resultat från ett större forskningsprojekt om utvecklingssamtal i förskolan. I intervjuer uttrycker föräldrar att de anser utvecklingssamtalen som meningsfulla på olika sätt. De kan säkerställa en känsla av tillit och trygghet med professionella pedagoger som i föräldrarnas ögon tycks framstå som ”barnexperter”. Vidare kan utvecklingssamtalen bidra till att bekräfta föräldrarnas egen bild av barnet och sitt föräldraskap

Förskoleföräldrars tankar om utvecklingssamtal

Hur upplever föräldrar utvecklingssamtal i förskolan? I denna artikel presenteras några resultat från ett större forskningsprojekt om utvecklingssamtal i förskolan. I intervjuer uttrycker föräldrar att de anser utvecklingssamtalen som meningsfulla på olika sätt. De kan säkerställa en känsla av tillit och trygghet med professionella pedagoger som i föräldrarnas ögon tycks framstå som ”barnexperter”. Vidare kan utvecklingssamtalen bidra till att bekräfta föräldrarnas egen bild av barnet och sitt föräldraskap

Secretor Status is Associated with Susceptibility to Disease in a Large GII.6 Norovirus Foodborne Outbreak

Norovirus is commonly associated with food and waterborne outbreaks. Genetic susceptibility to norovirus is largely dependent on presence of histo-blood group antigens (HBGA), specifically ABO, secretor, and Lewis phenotypes. The aim of the study was to determine the association between HBGAs to norovirus susceptibility during a large norovirus foodborne outbreak linked to genotype GII.6 in an office-based company in Stockholm, Sweden, 2015. A two-episode outbreak with symptoms of diarrhea and vomiting occurred in 2015. An online questionnaire was sent to all 1109 employees that had worked during the first outbreak episode. Food and water samples were collected from in-house restaurant and tested for bacterial and viral pathogens. In addition, fecal samples were collected from 8 employees that had diarrhea. To investigate genetic susceptibility during the outbreak, 98 saliva samples were analyzed for ABO, secretor, and Lewis phenotypes using ELISA. A total of 542 of 1109 (49%) employees reported gastrointestinal symptoms. All 8 fecal samples tested positive for GII norovirus, which was also detected in coleslaw collected from the in-house restaurant. Eating at the in-house restaurant was significantly associated with risk of symptom development. Nucleotide sequencing was successful for 5/8 fecal samples and all belonged to the GII.6 genotype. HBGA characterization showed a strong secretor association to norovirus-related symptoms (P = 0.014). No association between norovirus disease and ABO phenotypes was observed. The result of this study shows that non-secretors were significantly less likely to report symptoms in a large foodborne outbreak linked to the emerging GII.6 norovirus strain

Reactive precipitation of vaterite calcium carbonate microspheres in supercritical carbon dioxide-water dispersion by microfluidics

International audienceVaterite, a polymorphic form of precipitated calcium carbonate, is an interesting material for various applications such as formulation of drug delivery systems due to its nanoporous structure. One of the carbonation processes to obtain nanostructured microspheres of vaterite consists in mixing an aqueous calcium phase with a supercritical CO2 phase, resulting in a heterogeneous dispersion. In this study, a continuous microfluidic method has been evaluated to produce monodisperse porous vaterite microparticles. A high-pressure microfluidic set-up has been developed, revealing that the dimensions and the dispersity of the CaCO3 particles are not affected by pressure but can be decreased by increasing the flow rate of the scCO2 and aqueous phases or addition of polymers in the aqueous phase. These observations were shown not to be related to the degree of dispersion of each phase within the microfluidic channel but to the interaction of the polymer with the CaCO3 particles and to the depressurization step at the end of the channel