Shuffling of mobile genetic elements (MGEs) in successful healthcare-associated MRSA (HA-MRSA).

Methicillin-resistant Staphylococcus aureus (MRSA) CC22 SCCmecIV is a successful hospital-associated (HA-) MRSA, widespread throughout the world, and now the dominant clone in UK hospitals. We have recently shown that MRSA CC22 is a particularly fit clone, and it rose to dominance in a UK hospital at the same time as it began acquiring an increased range of antibiotic resistances. These resistances were not accumulated by individual CC22 isolates, but appear to shuffle frequently between isolates of the MRSA CC22 population. Resistances are often encoded on mobile genetic elements (MGEs) that include plasmids, transposons, bacteriophage and S. aureus pathogenicity islands (SaPIs). Using multi-strain whole genome microarrays, we show that there is enormous diversity of MGE carried within a MRSA CC22 SCCmecIV population, even among isolates from the same hospital and time period. MGE profiles were so variable that they could be used to track the spread of variant isolates within the hospital. We exploited this to show that the majority of patients colonised with MRSA at hospital admission that subsequently became infected were infected with their own colonising isolate. Our studies reveal MGE spread, stability, selection and clonal adaptation to the healthcare setting may be key to the success of HA-MRSA clones, presumably by allowing rapid adaptation to antibiotic exposure and new hosts

Quantum Parrondo's game with random strategies

We present a quantum implementation of Parrondo's game with randomly switched strategies using 1) a quantum walk as a source of ``randomness'' and 2) a completely positive (CP) map as a randomized evolution. The game exhibits the same paradox as in the classical setting where a combination of two losing strategies might result in a winning strategy. We show that the CP-map scheme leads to significantly lower net gain than the quantum walk scheme

High‑temperature structural phase transitions in neighborite: a high‑resolution neutron powder diffraction investigation

The nature of the apparently continuous structural phase transition at 1,049 K in the perovskite-structured, MgSiO3 isomorph, neighborite (NaMgF3), from the orthorhombic (Pbnm) hettotype phase to the cubic ( Pm3¯m ) aristotype structure, has been re-investigated using high-resolution, time-of-flight neutron powder diffraction. Using data collected at 1 K intervals close to the nominal phase transition temperature, the temperature dependence of the intensities of superlattice reflections at the M point (2πa[12,12,0]) and the R point (2πa[12,12,12]) of the pseudocubic Brillouin zone indicate the existence of a new intermediate tetragonal phase in space group P4/mbm, with a narrow phase field extending from ~1,046.5 to ~1,048.5 K, at ambient pressure. Group theoretical analysis shows that the structural transitions identified in this study, Pbnm–P4/mbm, and P4/mbm– Pm3¯m , are permitted to be second order. The observation of the tetragonal phase resolves the longstanding issue of why the high-temperature phase transition, previously identified as Pbnm– Pm3¯m , and which would be expected to be first order under Landau theory, is in fact found to be continuous. Analysis of the pseudocubic shear strain shows it to vary with a critical exponent of 0.5 implying that the phase transition from Pbnm to P4/mbm is tricritical in character. The large librational modes that exist in the MgF6 octahedron at high temperature, and the use of Gaussian probability density functions to describe atomic displacements, result in apparent bond shortening in the Mg–F distances, making mode amplitude determination an unreliable method for determination of the critical exponent from internal coordinates. Crystal structures are reported for the three phases of NaMgF3 at 1,033 K (Pbnm), 1,047 K (P4/mbm) and 1,049 K ( Pm3¯m )

Perturbed spiral real-time phase-contrast MR with compressive sensing reconstruction for assessment of flow in children

PURPOSE: we implemented a golden‐angle spiral phase contrast sequence. A commonly used uniform density spiral and a new ‘perturbed’ spiral that produces more incoherent aliases were assessed. The aim was to ascertain whether greater incoherence enabled more accurate Compressive Sensing reconstruction and superior measurement of flow and velocity. METHODS: A range of ‘perturbed’ spiral trajectories based on a uniform spiral trajectory were formulated. The trajectory that produced the most noise‐like aliases was selected for further testing. For in‐silico and in‐vivo experiments, data was reconstructed using total Variation L1 regularisation in the spatial and temporal domains. In‐silico, the reconstruction accuracy of the ‘perturbed’ golden spiral was compared to uniform density golden‐angle spiral. For the in‐vivo experiment, stroke volume and peak mean velocity were measured in 20 children using ‘perturbed’ and uniform density golden‐angle spiral sequences. These were compared to a reference standard gated Cartesian sequence. RESULTS: In‐silico, the perturbed spiral acquisition produced more accurate reconstructions with less temporal blurring (NRMSE ranging from 0.03 to 0.05) than the uniform density acquisition (NRMSE ranging from 0.06 to 0.12). This translated in more accurate results in‐vivo with no significant bias in the peak mean velocity (bias: −0.1, limits: −4.4 to 4.1 cm/s; P = 0.98) or stroke volume (bias: −1.8, limits: −9.4 to 5.8 ml, P = 0.19). CONCLUSION: We showed that a ‘perturbed’ golden‐angle spiral approach is better suited to Compressive Sensing reconstruction due to more incoherent aliases. This enabled accurate real‐time measurement of flow and peak velocity in children

Automated Suturing For Pacemaker Lead Placement Via Video Guided Minimally Invasive Surgical Access

The placement of permanent and temporary cardiac epicardial pacemaker leads through minimally invasive cardiac surgery (MICS) access remains a challenge. A reliable ergonomic approach for remote lead placement requires improved technology. We present a novel means to enable the remote placement of epicardial leads using automated suturing devices and videoscopy

Assessing heat pumps as flexible load

In a future power system featuring significant renewable generation, the ability to manipulate domestic demand through the flexible operation of heat-led technologies such as heat pumps and micro-combined heat and power could be a critical factor in providing a secure and stable supply of electrical energy. Using a simulation-based approach, this study examined the linkage between the thermal characteristics of buildings and the scope for flexibility in the operating times of air source heat pumps. This was assessed against the resulting impact on the end-user’s comfort and convenience. A detached dwelling and flat were modelled in detail along with their heating system in order to determine the temporal shift achievable in the heat pump operating times for present-day and future dwellings. The simulation results indicated that the scope for shifting heat pump operating times in the existing building stock was limited, with time shifts of only 1–2 h achieved before there was a serious impact on the comfort of the occupant. However, if insulation levels were dramatically improved and substantial levels of thermal buffering were added into the heating system, sizable time shifts of up to 6 h were achievable without a significant impact on either space or hot water temperatures

Rate pressure product

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73724/1/j.1365-2044.1980.tb05005.x.pd

Reduced exercise capacity in patients with systemic sclerosis is associated with lower peak tissue oxygen extraction: a cardiovascular magnetic resonance-augmented cardiopulmonary exercise study

Background: Exercise intolerance in systemic sclerosis (SSc) is typically attributed to cardiopulmonary limitations. However, problems with skeletal muscle oxygen extraction have not been fully investigated. This study used cardiovascular magnetic resonance (CMR)-augmented cardiopulmonary exercise testing (CMR-CPET) to simultaneously measure oxygen consumption and cardiac output. This allowed calculation of arteriovenous oxygen content gradient, a recognized marker of oxygen extraction. We performed CMR-CPET in 4 groups: systemic sclerosis (SSc); systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH); non-connective tissue disease pulmonary hypertension (NC-PAH); and healthy controls. Methods: We performed CMR-CPET in 60 subjects (15 in each group) using a supine ergometer following a ramped exercise protocol until exhaustion. Values for oxygen consumption, cardiac output and oxygen content gradient, as well as ventricular volumes, were obtained at rest and peak-exercise for all subjects. In addition, T1 and T2 maps were acquired at rest, and the most recent clinical measures (hemoglobin, lung function, 6-min walk, cardiac and catheterization) were collected. Results: All patient groups had reduced peak oxygen consumption compared to healthy controls (p<0.022). The SSc and SSc-PAH groups had reduced peak oxygen content gradient compared to healthy controls (p<0.03). Conversely, the SSc-PAH and NC-PH patients had reduced peak cardiac output compared to healthy controls and SSc patients (p<0.006). Higher hemoglobin was associated with higher peak oxygen content gradient (p=0.025) and higher myocardial T1 was associated with lower peak stroke volume (p=0.011). Conclusions: Reduced peak oxygen consumption in SSc patients is predominantly driven by reduced oxygen content gradient and in SSc-PAH patients this was amplifed by reduced peak cardiac output

Regulation of xanthine dehydrogensase gene expression and uric acid production in human airway epithelial cells

© 2017 Huff et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Introduction: The airway epithelium is a physical and immunological barrier that protects the pulmonary system from inhaled environmental insults. Uric acid has been detected in the respiratory tract and can function as an antioxidant or damage associated molecular pattern. We have demonstrated that human airway epithelial cells are a source of uric acid. Our hypothesis is that uric acid production by airway epithelial cells is induced by environmental stimuli associated with chronic respiratory diseases. We therefore examined how airway epithelial cells regulate uric acid production. Materials and methods: Allergen and cigarette smoke mouse models were performed using house dust mite (HDM) and cigarette smoke exposure, respectively, with outcome measurements of lung uric acid levels. Primary human airway epithelial cells isolated from clinically diagnosed patients with asthma and chronic obstructive pulmonary disease (COPD) were grown in submerged cultures and compared to age-matched healthy controls for uric acid release. HBEC-6KT cells, a human airway epithelial cell line, were grown under submerged monolayer conditions for mechanistic and gene expression studies. Results: HDM, but not cigarette smoke exposure, stimulated uric acid production in vivo and in vitro. Primary human airway epithelial cells from asthma, but not COPD patients, displayed elevated levels of extracellular uric acid in culture. In HBEC-6KT, production of uric acid was sensitive to the xanthine dehydrogenase (XDH) inhibitor, allopurinol, and the ATP Binding Cassette C4 (ABCC4) inhibitor, MK-571. Lastly, the pro-inflammatory cytokine combination of TNF-α and IFN-γ elevated extracellular uric acid levels and XDH gene expression in HBEC-6KT cells. Conclusions: Our results suggest that the active production of uric acid from human airway epithelial cells may be intrinsically altered in asthma and be further induced by pro-inflammatory cytokines

An unexpected disruption of the atmospheric quasi-biennial oscillation

This is the author accepted manuscript. The final version is available from AAAS via the DOI in this recordWe thank the European Centre for Medium-Range Weather Forecasts for providing ERA-Interim and Operational Analysis data (www.ecmwf.int/en/forecasts) and the Freie Universität Berlin for providing radiosonde data (www.geo.fu-berlin.de/en/met/ag/strat/produkte/qbo). The CMIP5 data was obtained from the British Atmospheric Data Centre (browse.ceda.ac.uk/browse/badc/cmip5). A summary of data used in the study is listed in table S1.One of the most repeatable phenomena seen in the atmosphere, the quasi-biennial oscillation (QBO) between prevailing eastward and westward wind jets in the equatorial stratosphere (approximately 16 to 50 kilometers altitude), was unexpectedly disrupted in February 2016. An unprecedented westward jet formed within the eastward phase in the lower stratosphere and cannot be accounted for by the standard QBO paradigm based on vertical momentum transport. Instead, the primary cause was waves transporting momentum from the Northern Hemisphere. Seasonal forecasts did not predict the disruption, but analogous QBO disruptions are seen very occasionally in some climate simulations. A return to more typical QBO behavior within the next year is forecast, although the possibility of more frequent occurrences of similar disruptions is projected for a warming climate.S.M.O. was supported by UK Natural Environment Research Council grants NE/M005828/1 and NE/P006779/1. A.A.S., J.R.K., and N.B. were supported by the Joint UK Business, Energy and Industrial Strategy/Defra Met Office Hadley Centre Climate Programme (GA01101). A.A.S. and J.R.K. were additionally supported by the EU Seventh Framework Programme SPECS (Seasonal-to-decadal climate Prediction for the improvement of European Climate Services) project