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The small quinolone derived compound HT61 enhances the effect of tobramycin against Pseudomonas aeruginosa in vitro and in vivo.
HT61 is a small quinolone-derived compound previously demonstrated to exhibit bactericidal activity against gram-positive bacteria including methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA). When combined with the classical antibiotics and antiseptics neomycin, gentamicin, mupirocin and chlorhexidine, HT61 demonstrated synergistic bactericidal activity against both MSSA and MRSA infections in vitro. In this study, we investigated the individual antimicrobial activity of HT61 alongside its capability to increase the efficacy of tobramycin against both a tobramycin sensitive laboratory reference strain (PAO1) and tobramycin resistant clinical isolates (RP73, NN2) of the gram-negative bacteria Pseudomonas aeruginosa (P. aeruginosa). Using broth microdilution methods, the MICs of HT61 against all strains were assessed, as well as the effect of HT61 in combination with tobramycin using both the chequerboard method and bacterial time-kill assays. A murine model of pulmonary infection was also used to evaluate the combination therapy of tobramycin and HT61 in vivo. In these studies, we demonstrated significant synergism between HT61 and Tobramycin against the tobramycin resistant P. aeruginosa strains RP73 and NN2, whilst an additive/intermediate effect was observed for P. aeruginosa strain PA01 which was further confirmed using bacterial time kill analysis. In addition, the enhancement of tobramycin by HT61 was also evident in in vitro assays of biofilm eradication. Finally, in vivo studies revealed analogous effects to those observed in vitro with HT61 when administered in combination with tobramycin against each of the three P. aeruginosa strains at the highest tested dose (10 mg/kg)
Time-frequency analysis of somatosensory evoked potentials for intraoperative spinal cord monitoring
PURPOSE: To evaluate the potential use of time-frequency analysis and its reliability in intraoperative somatosensory evoked potential (SEP) monitoring. METHODS: One hundred ninety-one patients undergoing thoracic and/or lumbar spinal surgery were studied retrospectively. The SEP signals were recorded during different stages of surgery. Averaged SEP was analyzed by short-time Fourier transform. The main peak in the time-frequency interpretation of SEP was measured in peak power, peak time, and peak frequency. The variability of these parameters was compared with that of amplitude and latency during different stages of surgery. The reliability of these parameters was also compared in true-positive and false-positive cases. RESULTS: During different surgical stages for the posterior tibial nerve SEP, the intrasubject variability of peak power was found to be more stable than that of amplitude, while the intrasubject variability of peak time did not show any difference compared with that of latency. The peak frequency presented stable during surgery. Moreover, the true-positive SEP case showed that peak power may detect the potential injury earlier than amplitude does. The false-positive outcomes could be reduced by the proposed method. CONCLUSIONS: The SEP peak component was found stable and reliable during the different stages of surgery. For clinical application purpose, time-frequency analysis was suggested to be an additional monitoring method besides the conventional amplitude/latency measurement since it provided a more reproducible and prompt response to the potential injury in intraoperative SEP monitoring. Copyright © 2011 by the American Clinical Neurophysiology Society.postprin
Vectorial dissipative solitons in vertical-cavity surface-emitting Lasers with delays
We show that the nonlinear polarization dynamics of a vertical-cavity
surface-emitting laser placed into an external cavity leads to the formation of
temporal vectorial dissipative solitons. These solitons arise as cycles in the
polarization orientation, leaving the total intensity constant. When the cavity
round-trip is much longer than their duration, several independent solitons as
well as bound states (molecules) may be hosted in the cavity. All these
solutions coexist together and with the background solution, i.e. the solution
with zero soliton. The theoretical proof of localization is given by the
analysis of the Floquet exponents. Finally, we reduce the dynamics to a single
delayed equation for the polarization orientation allowing interpreting the
vectorial solitons as polarization kinks.Comment: quasi final resubmission version, 12 pages, 9 figure
Time separation as a hidden variable to the Copenhagen school of quantum mechanics
The Bohr radius is a space-like separation between the proton and electron in
the hydrogen atom. According to the Copenhagen school of quantum mechanics, the
proton is sitting in the absolute Lorentz frame. If this hydrogen atom is
observed from a different Lorentz frame, there is a time-like separation
linearly mixed with the Bohr radius. Indeed, the time-separation is one of the
essential variables in high-energy hadronic physics where the hadron is a bound
state of the quarks, while thoroughly hidden in the present form of quantum
mechanics. It will be concluded that this variable is hidden in Feynman's rest
of the universe. It is noted first that Feynman's Lorentz-invariant
differential equation for the bound-state quarks has a set of solutions which
describe all essential features of hadronic physics. These solutions explicitly
depend on the time separation between the quarks. This set also forms the
mathematical basis for two-mode squeezed states in quantum optics, where both
photons are observable, but one of them can be treated a variable hidden in the
rest of the universe. The physics of this two-mode state can then be translated
into the time-separation variable in the quark model. As in the case of the
un-observed photon, the hidden time-separation variable manifests itself as an
increase in entropy and uncertainty.Comment: LaTex 10 pages with 5 figure. Invited paper presented at the
Conference on Advances in Quantum Theory (Vaxjo, Sweden, June 2010), to be
published in one of the AIP Conference Proceedings serie
A mathematical model for breath gas analysis of volatile organic compounds with special emphasis on acetone
Recommended standardized procedures for determining exhaled lower respiratory
nitric oxide and nasal nitric oxide have been developed by task forces of the
European Respiratory Society and the American Thoracic Society. These
recommendations have paved the way for the measurement of nitric oxide to
become a diagnostic tool for specific clinical applications. It would be
desirable to develop similar guidelines for the sampling of other trace gases
in exhaled breath, especially volatile organic compounds (VOCs) which reflect
ongoing metabolism. The concentrations of water-soluble, blood-borne substances
in exhaled breath are influenced by: (i) breathing patterns affecting gas
exchange in the conducting airways; (ii) the concentrations in the
tracheo-bronchial lining fluid; (iii) the alveolar and systemic concentrations
of the compound. The classical Farhi equation takes only the alveolar
concentrations into account. Real-time measurements of acetone in end-tidal
breath under an ergometer challenge show characteristics which cannot be
explained within the Farhi setting. Here we develop a compartment model that
reliably captures these profiles and is capable of relating breath to the
systemic concentrations of acetone. By comparison with experimental data it is
inferred that the major part of variability in breath acetone concentrations
(e.g., in response to moderate exercise or altered breathing patterns) can be
attributed to airway gas exchange, with minimal changes of the underlying blood
and tissue concentrations. Moreover, it is deduced that measured end-tidal
breath concentrations of acetone determined during resting conditions and free
breathing will be rather poor indicators for endogenous levels. Particularly,
the current formulation includes the classical Farhi and the Scheid series
inhomogeneity model as special limiting cases.Comment: 38 page
Circuit Quantum Electrodynamics with a Spin Qubit
Circuit quantum electrodynamics allows spatially separated superconducting
qubits to interact via a "quantum bus", enabling two-qubit entanglement and the
implementation of simple quantum algorithms. We combine the circuit quantum
electrodynamics architecture with spin qubits by coupling an InAs nanowire
double quantum dot to a superconducting cavity. We drive single spin rotations
using electric dipole spin resonance and demonstrate that photons trapped in
the cavity are sensitive to single spin dynamics. The hybrid quantum system
allows measurements of the spin lifetime and the observation of coherent spin
rotations. Our results demonstrate that a spin-cavity coupling strength of 1
MHz is feasible.Comment: Related papers at http://pettagroup.princeton.edu
Coverage, Continuity and Visual Cortical Architecture
The primary visual cortex of many mammals contains a continuous
representation of visual space, with a roughly repetitive aperiodic map of
orientation preferences superimposed. It was recently found that orientation
preference maps (OPMs) obey statistical laws which are apparently invariant
among species widely separated in eutherian evolution. Here, we examine whether
one of the most prominent models for the optimization of cortical maps, the
elastic net (EN) model, can reproduce this common design. The EN model
generates representations which optimally trade of stimulus space coverage and
map continuity. While this model has been used in numerous studies, no
analytical results about the precise layout of the predicted OPMs have been
obtained so far. We present a mathematical approach to analytically calculate
the cortical representations predicted by the EN model for the joint mapping of
stimulus position and orientation. We find that in all previously studied
regimes, predicted OPM layouts are perfectly periodic. An unbiased search
through the EN parameter space identifies a novel regime of aperiodic OPMs with
pinwheel densities lower than found in experiments. In an extreme limit,
aperiodic OPMs quantitatively resembling experimental observations emerge.
Stabilization of these layouts results from strong nonlocal interactions rather
than from a coverage-continuity-compromise. Our results demonstrate that
optimization models for stimulus representations dominated by nonlocal
suppressive interactions are in principle capable of correctly predicting the
common OPM design. They question that visual cortical feature representations
can be explained by a coverage-continuity-compromise.Comment: 100 pages, including an Appendix, 21 + 7 figure
Acute kidney disease and renal recovery : consensus report of the Acute Disease Quality Initiative (ADQI) 16 Workgroup
Consensus definitions have been reached for both acute kidney injury (AKI) and chronic kidney disease (CKD) and these definitions are now routinely used in research and clinical practice. The KDIGO guideline defines AKI as an abrupt decrease in kidney function occurring over 7 days or less, whereas CKD is defined by the persistence of kidney disease for a period of > 90 days. AKI and CKD are increasingly recognized as related entities and in some instances probably represent a continuum of the disease process. For patients in whom pathophysiologic processes are ongoing, the term acute kidney disease (AKD) has been proposed to define the course of disease after AKI; however, definitions of AKD and strategies for the management of patients with AKD are not currently available. In this consensus statement, the Acute Disease Quality Initiative (ADQI) proposes definitions, staging criteria for AKD, and strategies for the management of affected patients. We also make recommendations for areas of future research, which aim to improve understanding of the underlying processes and improve outcomes for patients with AKD
An empirical examination of the factor structure of compassion
Compassion has long been regarded as a core part of our humanity by contemplative traditions, and in recent years, it has received growing research interest. Following a recent review of existing conceptualisations, compassion has been defined as consisting of the following five elements: 1) recognising suffering, 2) understanding the universality of suffering in human experience, 3) feeling moved by the person suffering and emotionally connecting with their distress, 4) tolerating uncomfortable feelings aroused (e.g., fear, distress) so that we remain open to and accepting of the person suffering, and 5) acting or being motivated to act to alleviate suffering. As a prerequisite to developing a high quality compassion measure and furthering research in this field, the current study empirically investigated the factor structure of the five-element definition using a combination of existing and newly generated self-report items. This study consisted of three stages: a systematic consultation with experts to review items from existing self-report measures of compassion and generate additional items (Stage 1), exploratory factor analysis of items gathered from Stage 1 to identify the underlying structure of compassion (Stage 2), and confirmatory factor analysis to validate the identified factor structure (Stage 3). Findings showed preliminary empirical support for a five-factor structure of compassion consistent with the five-element definition. However, findings indicated that the ‘tolerating’ factor may be problematic and not a core aspect of compassion. This possibility requires further empirical testing. Limitations with items from included measures lead us to recommend against using these items collectively to assess compassion. Instead, we call for the development of a new self-report measure of compassion, using the five-element definition to guide item generation. We recommend including newly generated ‘tolerating’ items in the initial item pool, to determine whether or not factor-level issues are resolved once item-level issues are addressed
Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector
Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02 TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1 μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos2Δϕ modulation for all ΣETPb ranges and particle pT
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