We describe here efforts to create and study magnetized electron–positron pair plasmas, the existence of which in astrophysical environments is well-established. Laboratory incarnations of such ...systems are becoming ever more possible due to novel approaches and techniques in plasma, beam and laser physics. Traditional magnetized plasmas studied to date, both in nature and in the laboratory, exhibit a host of different wave types, many of which are generically unstable and evolve into turbulence or violent instabilities. This complexity and the instability of these waves stem to a large degree from the difference in mass between the positively and the negatively charged species: the ions and the electrons. The mass symmetry of pair plasmas, on the other hand, results in unique behaviour, a topic that has been intensively studied theoretically and numerically for decades, but experimental studies are still in the early stages of development. A levitated dipole device is now under construction to study magnetized low-energy, short-Debye-length electron–positron plasmas; this experiment, as well as a stellarator device that is in the planning stage, will be fuelled by a reactor-based positron source and make use of state-of-the-art positron cooling and storage techniques. Relativistic pair plasmas with very different parameters will be created using pair production resulting from intense laser–matter interactions and will be confined in a high-field mirror configuration. We highlight the differences between and similarities among these approaches, and discuss the unique physics insights that can be gained by these studies.
•Significant increase in fully susceptible E. coli after reduced antimicrobial use.•Multidrug resistant E. coli decline significantly after withdrawing group treatment.•However, resistant commensal ...E. coli remain after withdrawal of group treatment.•Resistant E. coli survived pen cleaning and could be detected on farm equipment.•Plasmids have an important role for the maintenance and dissemination of resistance.
An important element in the control of antimicrobial resistance (AMR) is reduction in antimicrobial usage. In the veterinary sector individual antimicrobial treatment of livestock, rather than the use of group treatment, can help achieve this goal. The aim of this study was to investigate how cessation of group antimicrobial treatment impacted the prevalence of AMR in commensal Escherichia coli in pigs at one farm over an 11-month period. Minimum inhibitory concentrations of eight antimicrobials were determined for 259 E. coli isolates collected during the study. A significant reduction in the prevalence of multidrug resistance and a significant increase in the proportion of full susceptibility to the panel of nine antimicrobials tested was seen after 11 months. Whole genome sequencing of 48 multidrug resistant isolates revealed E. coli clones that persisted across multiple visits and provided evidence for the presence of plasmids harbouring AMR genes shared across multiple E. coli lineages. E. coli were also isolated from on-farm environmental samples. Whole genome sequencing of one multidrug resistant isolate obtained from cleaning tools showed it was clonal to pig-derived E. coli that persisted on the farm for 11 months. In this study we provide evidence that withdrawal of group antimicrobial use leads to significant reductions in key indicators for AMR prevalence and the importance of the farm environment as a reservoir of resistant bacteria. These findings support policy makers and producers in the implementation of measures to control AMR and reduce antimicrobial use.
•A broth dilution procedure for AST of Brachyspira species is described.•The broth dilution method was validated in a ring trial.•Intra- and inter-laboratory reproducibility was good.•New control ...strains are proposed.•Increased MIC corresponded to genomic data indicating decreased susceptibility.
Brachyspira hyodysenteriae and Brachyspira pilosicoli cause economically important enteric disease in pigs. Treatment of these infections often includes antimicrobial administration, which can be most effective when therapeutic options are informed by antimicrobial susceptibility testing data. Here we describe a method for broth dilution antimicrobial susceptibility testing of these bacteria, both of which are difficult to culture in vitro. The protocol was evaluated for its fitness for use in an inter-laboratory ring trial involving eight laboratories from seven countries, and employing eleven test strains (5 Brachyspira hyodysenteriae including the type strain B78T and 6 Brachyspira pilosicoli) and six antibiotics. Overall intra- and inter-laboratory reproducibility of this method was very good (>90 % MICs at mode +/- 1 log2). Whole genome sequencing revealed good correspondence between reduced susceptibility and the presence of previously defined antimicrobial resistance determinants. Interestingly, lnu(C) was identified in B. pilosicoli isolates with elevated MICs of lincomycin, whilst tva(B) was associated with elevated MICs of pleuromutilins in this species. We designated two new control strains with MICs lying within currently tested ranges, including for the pleuromutilins, in contrast to the control strain B. hyodysenteriae B78T. These were deposited at the DSMZ-German Collection of Microorganisms and Cell Cultures GmbH. The validation of a standard protocol and identification of new control strains facilitates comparisons between studies, establishment of robust interpretative criteria, and ultimately contributes to rational antimicrobial use when treating infected livestock.
Efforts are underway to magnetically confine electron–positron pair plasmas to study their unique behaviour, which is characterized by significant changes in plasma time and length scales, supported ...waves and unstable modes. However, use of conventional plasma diagnostics presents challenges with these low-density and annihilating matter–antimatter plasmas. To address this problem, we propose to develop techniques based on the distinct emission provided by annihilation. This emission exhibits two spatial correlations: the distance attenuation of isotropic sources and the back-to-back propagation of momentum-preserving 2$\gamma$ annihilation. We present the results of our analysis of the $\gamma$ emission rate and the spatial profile of the annihilation in a magnetized pair plasma from direct pair collisions, from the formation and decay of positronium as well as from transport processes. In order to demonstrate the effectiveness of annihilation-based techniques, we tested them on annular $\gamma$ emission profiles produced by a $\beta ^+$ radioisotope on a rotating turntable. Direct and positronium-mediated annihilation result in overlapping volumetric $\gamma$ sources, and the 2$\gamma$ emission from these volumetric sources can be tomographically reconstructed from coincident counts in multiple detectors. Transport processes result in localized annihilation where field lines intersect walls, limiters or internal magnets. These localized sources can be identified by the fractional $\gamma$ counts on spatially distributed detectors.
Abstract Background Our purpose was to assess the prevalence and clinical implications of left ventricular (LV) and right ventricular (RV) diastolic dysfunction (DD) in patients with repaired ...tetralogy of Fallot (TOF). Methods Adults with repaired TOF at 11 North American congenital heart disease centres were included. Of 556 patients analyzed, 325 had sufficient Doppler data to evaluate for LV DD, defined as mitral lateral e′ < 10 cm/s and E/e′ ratio > 9. Abnormal RV diastolic function was defined as tricuspid E/A ratio of 0.8 to 2.1 with E/e′ ratio > 6 or a tricuspid ratio E/A > 2.1 with a deceleration time < 120 milliseconds, and 105 patients were found to have sufficient Doppler data. Results Abnormal LV diastolic Doppler indices were prevalent in 13.8% and associated with hypertension, dyslipidemia, 3 or more cardiac operations, and a history of ventricular tachycardia. Abnormal RV indices were prevalent in 52.4% and associated with hypertension, dyslipidemia, diabetes mellitus, and 3 or more cardiac operations. Ventricular tachycardia was more common in those with abnormal RV diastolic function. Conclusion Further prospective studies are needed to evaluate these associations with DD and the impact of treatment risk factors on diastolic function and arrhythmia burden.
The aim of this study was to assess the impact of ciprofloxacin, clindamycin, and placebo administration on culturable Gram-negative isolates and the antibiotic resistance genes they harbor. Saliva ...and fecal samples were collected from healthy human volunteers before and at intervals, up to 1 year after antibiotic administration. Samples were plated on selective and nonselective media to monitor changes in different colony types or bacterial species. Following ciprofloxacin administration, there was a decrease of Escherichia coli in feces and after clindamycin administration a decrease of Bacteroides in feces and Leptotrichia in saliva, which all returned to pretreatment levels within 1 to 4 months. Ciprofloxacin administration also resulted in an increase in ciprofloxacin-resistant Veillonella in saliva, which persisted for 12 months. Additionally, 949 aerobic and anaerobic isolates purified from ciprofloxacin- and clindamycin-containing plates were screened for the presence of resistance genes. Resistance gene carriage was widespread in isolates from all three treatment groups, and no association was observed between genes and antibiotic administration. Although the anaerobic component of the microbiota was not a major reservoir of aerobe-associated antimicrobial resistance (AMR) genes, we detected the sulfonamide resistance gene sul2 in anaerobic isolates. The longitudinal nature of the study allowed identification of distinct Escherichia coli clones harboring multiple resistance genes, including one carrying an extended-spectrum β-lactamase blaCTX-M group 9 gene, which persisted in the gut for up to 4 months. This study provided insight into the effects of antibiotic administration on healthy microbiota and the diversity of resistance genes harbored therein.
Regulatory T cells, a subset of CD4+ T lymphocytes, play a pivotal role in the maintenance of the balance between the tissue-damaging and protective effects of the immune response. These cells have ...immunosuppressive function and have been intensely studied in the context of autoimmunity, cancer, allergies, asthma, and infectious diseases. Their role in chronic and persistent viral infections is well appreciated. In acute viral infections, the function of these cells is still unclear. The host and pathogen factors that control the generation and activity of regulatory T cells and the role of these cells in modulating expansion, contraction, and development of immune memory in acute respiratory virus infection need to be further elucidated.
The southern Rae Province of the western Canadian Shield underwent extensive reworking during Paleoproterozoic time. Widespread granitic plutonism and poorly defined metamorphism resulting from the ...ca. 2.5 to 2.3
Ga Arrowsmith Orogen was followed by more intense thermotectonic overprints attributed to the 1.99–1.92
Ga Taltson Orogen in the west and ca. 1.91–1.90
Ga tectonic activity associated with the Snowbird Tectonic Zone in the east. The Thluicho Lake Group is a fining-upwards, conglomerate–arkose–argillite succession deposited in an intermontane setting towards the end of the Taltson Orogen. Following deposition, the Thluicho Lake Group underwent two phases of regional folding and greenschist-facies metamorphism marking the latest Taltson and Snowbird overprints, respectively, prior to the emplacement of extensive 1.82
Ga mafic dykes. These depositional constraints support correlation of the Thluicho Lake Group with the lithologically similar Nonacho Group in the Northwest Territories, whereas petrological similarities and coeval emplacement ages indicate that the mafic dykes represent a southeastward extension of the Sparrow dykes.
Mafic volcanic rocks geochemically linked to the dykes are intercalated within the Martin Group, a continental redbed succession deposited in trans-tensional basin settings, indicating that deposition was ongoing at 1.82
Ga. Similarities in age, lithological association and depositional setting suggest that the Martin Group is broadly correlative with the Baker Lake Group of the lower Dubawnt Supergroup in Nunavut. Widespread lamprophyre dykes of the type that fed minette volcanic rocks of the Christopher Island Formation in the Baker Lake Group are also spatially associated with the Martin Group. The broadly coeval Hudson granites, which extend over much of the same ground as the lamprophyres in Nunavut, also appear to have analogs in the southern Rae Province.
The formation of widespread trans-tensional basins, together with extensive dyke emplacement, implies a period of intense brittle to brittle–ductile deformation throughout the western Churchill Province at about 1.83–1.82
Ga. This deformation is attributed to a broadly east-west stress regime imposed by accretion of the Nahanni-Fort Simpson Terrane to the west, combined with terminal collision in the Trans-Hudson Orogen to the east.
Antiplatelet therapy is the mainstay of the treatment and secondary prevention of cardiovascular and cerebrovascular ischemic events. We assessed the safety, tolerability, and pharmacodynamics of ...lotrafiban, an oral platelet glycoprotein IIb/IIIa inhibitor, as a secondary prevention strategy in patients with cerebrovascular or cardiovascular disease.
Overall, 451 patients with a recent cardiovascular or cerebrovascular acute ischemic event were randomized in a double-blind fashion to 1 of 5 dosing regimens for 12 weeks: placebo or 5, 20, 50, or 100 mg lotrafiban, both twice daily with 300 to 325 mg/d aspirin. The primary end point was the incidence and tolerability of major and minor bleeding during treatment. Secondary end points included inhibition of platelet aggregation and clinical events. The placebo and lotrafiban 5-mg groups had similarly low rates of minor and major bleeding, but the 100-mg arm was terminated early because of excess major bleeding. Protocol-defined thrombocytopenia (<100 000 platelets/microL) occurred in 5 lotrafiban-treated patients (1.4%, 95% CI 0.2% to 2.7%) and 1 placebo patient (1.1%, 95% CI 0% to 3.1%). Three lotrafiban-treated patients had a nadir platelet count <20 000/microL (0.9%, 95% CI 0% to 1.8%). Lotrafiban produced dose-dependent inhibition of platelet aggregation; 5 mg lotrafiban did not differ significantly from placebo, whereas 100 mg inhibited aggregation by nearly 100%.
-Lotrafiban provides dose-dependent platelet inhibition when administered to a range of patients with atherosclerosis. The level of platelet inhibition appears to correlate with bleeding risk and drug tolerability.
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