Currently licensed influenza vaccines mainly induce antibodies against highly variable epitopes. Due to antigenic drift, protection is subtype or strain-specific and regular vaccine updates are ...required. In case of antigenic shifts, which have caused several pandemics in the past, completely new vaccines need to be developed. We set out to develop a vaccine that provides protection against a broad range of influenza viruses. Therefore, highly conserved parts of the influenza A virus (IAV) were selected of which we constructed antibody and T cell inducing peptide-based vaccines. The B epitope vaccine consists of the highly conserved HA2 fusion peptide and M2e peptide coupled to a CD4 helper epitope. The T epitope vaccine comprises 25 overlapping synthetic long peptides of 26-34 amino acids, thereby avoiding restriction for a certain MHC haplotype. These peptides are derived from nucleoprotein (NP), polymerase basic protein 1 (PB1) and matrix protein 1 (M1). C57BL/6 mice, BALB/c mice, and ferrets were vaccinated with the B epitopes, 25 SLP or a combination of both. Vaccine-specific antibodies were detected in sera of mice and ferrets and vaccine-specific cellular responses were measured in mice. Following challenge, both mice and ferrets showed a reduction of virus titers in the lungs in response to vaccination. Summarizing, a peptide-based vaccine directed against conserved parts of influenza virus containing B and T cell epitopes shows promising results for further development. Such a vaccine may reduce disease burden and virus transmission during pandemic outbreaks.
Background: The total number of people with dementia symptoms is expected to double every 20 years and there will also be an increase in the number of older immigrants in several countries. There are ...considerable deficiencies in the present knowledge of how to conduct well-functioning health care for immigrants with dementia symptoms. The aim of this study was to explore caring and uncaring encounters between assistant nurses and immigrants in two group homes for persons with dementia symptoms in Sweden: a Finnish-speaking as well as a Swedish-speaking context. In addition, this study aims to describe how caring and uncaring encounters are manifested in
these
two contexts according to Halldórsdóttir’s theory of “Caring and Uncaring encounters”. Method: Descriptive field notes from 30 separate observations were analyzed using qualitative deductive content analysis. Results: The main category “caring encounters” focused on reaching out to initiate connection through communication, removing masks of anonymity by acknowledging the unique person, acknowledgment of connection by being personal. Reaching a level of truthfulness by being present and showing respect, raising the level of solidarity by equality and true negotiation of care, based on the residents’ needs. The main category, uncaring encounters, focused on disinterest in and insensitivity towards the other, coldness in the connection and lack of humanity in care situations. The observations showed that caring encounters occurred more in the Finnish-speaking context and uncaring encounters more often in the Swedish context
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Conclusion: Encounters could be caring, uncaring, and carried out using a person-centered approach. Communication and relationships could be facilitated using the same language but also through learning to interpret residents’ needs and desires.
Experiments based on noble elements such as gaseous or liquid argon or xenon utilize the ionization and scintillation properties of the target materials to detect radiation-induced recoils. A ...requirement for high light and charge yields is to reduce electronegative impurities well below the ppb (parts per billion, 1 ppb
=
1
×
10
-
9
mol/mol) level. To achieve this, the target material is continuously circulated in the gas phase through a purifier and returned to the detector. Additionally, the low backgrounds necessary dictate low-Rn-emanation rates from all components that contact the gas. Since commercial pumps often introduce electronegative impurities from lubricants on internal components or through small air leaks, and are not designed to meet the radiopurity requirements, custom-built pumps are an advantageous alternative. A new pump has been developed in Muenster in cooperation with the nEXO group at Stanford University and the nEXO/XENON group at Rensselaer Polytechnic Institute based on a magnetically-coupled piston in a hermetically sealed low-Rn-emanating vessel. This pump delivers high performance for noble gases, reaching more than 210 standard liters per minute (slpm) with argon and more than 170 slpm with xenon while maintaining a compression of up to 1.9 bar, demonstrating its capability for noble gas detectors and other applications requiring high standards of gas purity.
Personalized dosimetry in computed tomography (CT) can be realized by a full Monte Carlo (MC) simulation of the scan procedure. Essential input data needed for the simulation are appropriate CT x-ray ...source models and a model of the patient's body which is based on the CT image. The purpose of this work is to develop comprehensive procedures for the determination of CT x-ray source models and their verification by comparison of calculated and measured dose distributions in physical phantoms. Mobile equipment together with customized software was developed and used for non-invasive determination of equivalent source models of CT scanners under clinical conditions. Standard and physical anthropomorphic CT dose phantoms equipped with real-time CT dose probes at five representative positions were scanned. The accumulated dose was measured during the scan at the five positions. ImpactMC, an MC-based CT dose software program, was used to simulate the scan. The necessary inputs were obtained from the scan parameters, from the equivalent source models and from the material-segmented CT images of the phantoms. 3D dose distributions in the phantoms were simulated and the dose values calculated at the five positions inside the phantom were compared to measured dose values. Initial results were obtained by means of a General Electric Optima CT 660 and a Toshiba (Canon) Aquilion ONE. In general, the measured and calculated dose values were within relative uncertainties that had been estimated to be less than 10%. The procedures developed were found to be viable and rapid. The procedures are applicable to any scanner type under clinical conditions without making use of the service mode with stationary x-ray tube position. Results show that the procedures are well suited for determining and verifying the equivalent source models needed for personalized CT dosimetry based on post-scan MC calculations.
Abstract
The study aimed to implement realistic source models of a computed tomography (CT) scanner and Monte Carlo simulations to actual patient data and to calculate patient-specific organ and ...effective dose estimates for patients undergoing dynamic CT myocardial perfusion examinations. Source models including bowtie filter, tube output and x-ray spectra were determined for a dual-source Siemens Somatom Definition Flash scanner. Twenty CT angiography patient datasets were merged with a scaled International Commission on Radiological Protection (ICRP) 110 voxel phantom. Dose simulations were conducted with ImpactMC software. Effective dose estimates varied from 5.0 to 14.6 mSv for the 80 kV spectrum and from 8.9 to 24.7 mSv for the 100 kV spectrum. Significant differences in organ doses and effective doses between patients emphasise the need to use actual patient data merged with matched anthropomorphic anatomy in the dose simulations to achieve a reasonable level of accuracy in the dose estimation procedure.
The genus Podaxis was first described from India by Linnaeus in 1771, but several revisions of the genus have left the taxonomy unclear. Forty-four Podaxis species names and nine intraspecific ...varieties are currently accepted, but most fungarium specimens are labelled Podaxis pistillaris . Recent molecular analyses based on barcoding genes suggest that the genus comprises several species, but their status is largely unresolved. Here we obtained basidiospores and photographs from 166 fungarium specimens from around the world and generated a phylogeny based on rDNA internal transcribed spacer ITS1, 5.8S and ITS2 (ITS), and a phylogenomic analysis of 3 839 BUSCO genes from low-coverage genomes for a subset of the specimens. Combining phylogenetics, phylogenomics, morphology, ecology, and geographical distribution, spanning 250 years of collections, we propose that the genus includes at least 16 unambiguous species. Based on 10 type specimens (holotype, paratype, and syntype), four recorded species were confirmed, P. carcinomalis , P. deflersii , P. emerici , and P. farlowii . Comparing phylogenetic analysis with described species, including morphology, ecology, and distribution, we resurrected P. termitophilus and designated neotypes, epitypes, or lectotypes for five previously described species, P. aegyptiacus , P. africana , P. beringamensis , P. calyptratus , and P. perraldieri . Lastly, based on phylogenies and morphology of type material, we synonymized three reported species, P. algericus , P. arabicus , and P. rugospora with P. pistillaris , and described five new species that we named P. desolatus , P. inyoensis , P. mareebaensis , P. namaquensis , and P. namibensis .
During construction work (2017–2019), an increase in Aspergillus flavus infections was noted among pediatric patients, the majority of whom were receiving amphotericin B prophylaxis. Microsatellite ...genotyping was used to characterize the outbreak. A total of 153 A. flavus isolates of clinical and environmental origin were included. Clinical isolates included 140 from 119 patients. Eight patients were outbreak-related patients, whereas 111 were outbreak-unrelated patients from Danish hospitals (1994–2023). We further included four control strains. Nine A. flavus isolates were from subsequent air sampling in the outbreak ward (2022–2023). Typing followed Rudramurthy et al.(S. M. Rudramurthy, H. A. de Valk, A. Chakrabarti, J. Meis, and C. H. W. Klaassen, PLoS One 6:e16086, 2011, https://doi.org/10.1371/journal.pone.0016086). Minimum spanning tree (MST) and discriminant analysis of principal components (DAPC) were used for cluster analysis. DAPC analysis placed all 153 isolates in five clusters. Microsatellite marker pattern was clearly distinct for one cluster compared to the others. The same cluster was observed in an MST. This cluster included all outbreak isolates, air-sample isolates, and additional patient isolates from the outbreak hospital, previously undisclosed as outbreak related. The highest air prevalence of A. flavus was found in two technical risers of the outbreak ward, which were then sealed. Follow-up air samples were negative for A. flavus. Microsatellite typing defined the outbreak as nosocomial and facilitated the identification of an in-hospital source. Six months of follow-up air sampling was without A. flavus. Outbreak-related/non-related isolates were easily distinguished with DAPC and MST, as the outbreak clone’s distinct marker pattern was delineated in both statistical analyses. Thus, it could be a variant of A. flavus, with a niche ability to thrive in the outbreak-hospital environment.IMPORTANCEAspergillus flavus can cause severe infections and hospital outbreaks in immunocompromised individuals. Although lack of isogeneity does not preclude an outbreak, our study underlines the value of microsatellite genotyping in the setting of potential A. flavus outbreaks. Microsatellite genotyping documented an isogenic hospital outbreak with an internal source. This provided the “smoking gun” that prompted the rapid allocation of resources for thorough environmental sampling, the results of which guided immediate and relevant cleaning and source control measures. Consequently, we advise that vulnerable patients should be protected from exposure and that genotyping be included early in potential A. flavus outbreak investigations. Inspection and sampling are recommended at any site where airborne spores might disperse from. This includes rarely accessed areas where air communication to the hospital ward cannot be disregarded.
Control of the potato late blight pathogen Phytophthora infestans relies heavily on chemicals. The fungicide metalaxyl‐M (Mefenoxam) has played an important role in controlling the disease, but ...insensitivity to the fungicide in certain isolates is now of major concern. A genetic basis for resistance to metalaxyl suggests the possibility for linking resistance phenotypes to specific population genetic markers, but in order to do this, the population genetic structure and mode of reproduction in a population must first be well described. The dynamics of metalaxyl‐M resistance in the Danish population of P. infestans was characterized over the course of the 2013 growing season, as was the population genetic structure, using simple sequence repeat (SSR) genotypes and single nucleotide polymorphism (SNP)‐based mitochondrial haplotyping of over 80 isolates. Both mating types A1 and A2 were present in most fields, but tests for recombination showed that clonal reproduction dominates in Danish populations. Genotype was not linked to haplotype and no differentiation was observed at the haplotype level, but rather between fields. Resistance phenotypes were linked to specific SSR alleles, demonstrating the potential for a more precise SNP‐based marker system for predicting resistance to metalaxyl‐M.
Interferon gamma (IFN-γ) is a 28 kDa homodimeric cytokine that exhibits potent immunomodulatory, anti-proliferative, and antiviral properties. The protein is used to treat chronic granulomatous ...disease and malignant osteopetrosis, and it is under investigation as a treatment for a variety of cancer, fungal and viral diseases. IFN-γ has a short circulating half life in vivo, which necessitates frequent administration to patients. An unusual feature of IFN-γ is that the protein contains no native cysteines. To create a longer-acting and potentially more effective form of the protein, we introduced a cysteine residue into the IFN-γ coding sequence at amino acid position 103, which is located in a surface-exposed, non-helical region of the protein. The added cysteine residue served as the site for targeted modification of the protein with a cysteine-reactive polyethylene glycol (PEG) reagent. The recombinant protein was expressed in bacteria, purified and modified with 10, 20, and 40 kDa maleimide PEGs. The purified, PEGylated proteins had in vitro bioactivities comparable to IFN-γ, as measured using an in vitro cell growth inhibition assay. The PEGylated proteins displayed 20- to 32-fold longer half lives than IFN-γ in rats, and they were significantly more effective than IFN-γ at inhibiting growth of a human tumor xenograft in athymic mice.
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