Frequency drift characterization of a laser stabilized to an optical fiber delay line.

Lasers stabilized to optical fiber delay lines have been shown to deliver a comparable short-term (<1 s) frequency noise performance to that achieved by lasers stabilized to ultra-low expansion (ULE) cavities, once the linear frequency drift has been removed. However, for continuous stable laser operations, the drift can be removed only when it can be predicted, e.g., when it is linear over very long timescales. To date, such long-term behaviour of the frequency drift in fiber delay lines has not been, to the best of our knowledge, characterised. In this work we experimentally characterise the frequency drift of a laser stabilised to a 500 m-long optical fiber delay line over the course of several days. We show that the drift still follows the temperature variations even when the spool temperature is maintained constant with fluctuations below tens of mK. Consequently, the drift is not linear over long timescales, preventing a simple feed-forward compensation. However, here we show that the drift can be reduced by exploiting the high level of correlation between laser frequency and the fiber temperature. In our demonstration, by applying a frequency correction proportional to temperature readings, a calculated frequency drift of less than 16 Hz/s over the several days of our test was obtained, corresponding to a 23-fold improvement from uncorrected values.

Utility of fractional exhaled nitric oxide suppression as a prediction tool for progression to biologic therapy.

RATIONALE: The utility of fractional exhaled nitric oxide (F ENO) suppression (FeNOSuppT) to identify non-adherence to inhaled corticosteroid (ICS) treatment has previously been reported, but whether it can predict clinical outcome remains unclear. OBJECTIVES: We examined the utility of FeNOSuppT in prediction of progression to biologic agents or discharge from specialist care. METHODS: FeNOSuppT was measured at home using remote monitoring technology of inhaler use alongside daily F ENO measurement over 7 days. Long-term clinical outcomes in terms of progression to biologic agent or discharge from specialist care were compared for non-suppressors and suppressors. MEASUREMENTS AND MAIN RESULTS: Of the 162 subjects, 135 successfully completed the test with 81 (60%) positive F ENO suppression tests. Subjects with a negative FeNOSuppT were more likely to proceed to biologic therapy (39 of 54 patients, 72%) compared to those with a positive FeNOSuppT (35 of 81 patients, 43%, p=0.001). In subjects with a positive FeNOSuppT, predictors of progression to biologic therapy included higher dose of maintenance steroid at initial assessment and prior intensive care unit admission. These subjects had a significant rise in F ENO between post-suppression test and follow-up (median, 33 (IQR 25-55) versus 71 (IQR 24-114); p=0.009), which was not explained by altered corticosteroid dose. CONCLUSIONS: A negative FeNOSuppT correlates with progression to biologic therapy. A positive FeNOSuppT, with subsequent maintenance of "optimised" F ENO, predicts a subgroup of patients in whom asthma control is preserved with adherence to high-dose ICS/long-acting ß2 agonist and who can be discharged from specialist care.

Robust and accurate measurements of gold nanoparticle concentrations using UV-visible spectrophotometry.

This paper provides an empirical formula to calculate the extinction efficiencies of gold nanoparticles over the size range 1-1000 nm in fluids with refractive indexes which extend from n = 1 to n = 1.62. The formula contains a shape factor to account for nonspherical particles and aggregates. The empirical curves are fitted to values calculated from accurate Mie and T-Matrix theory and confirm previous descriptions which are restricted to nearly spherical particles in water of diameter between 5 and 100 nm. This paper demonstrates that these previous descriptions will be in error for fluids other than water and for nonspherical particles greater than 100 nm in size. An empirical description is provided which matches calculated values to within a few percent across most of the range. The description also matches experimental data to within the standard relative error, currently 5% at best, using other methods which directly measure the particle concentration. These extinction efficiencies can be used to validate the concentration of gold nanoparticles in a wide range of situations to support the drive for reproducibility in nanoparticle research.

Ultrastable laser interferometry for earthquake detection with terrestrial and submarine cables.

Detecting ocean-floor seismic activity is crucial for our understanding of the interior structure and dynamic behavior of Earth. However, 70% of the planet's surface is covered by water, and seismometer coverage is limited to a handful of permanent ocean bottom stations. We show that existing telecommunication optical fiber cables can detect seismic events when combined with state-of-the-art frequency metrology techniques by using the fiber itself as the sensing element. We detected earthquakes over terrestrial and submarine links with lengths ranging from 75 to 535 kilometers and a geographical distance from the earthquake's epicenter ranging from 25 to 18,500 kilometers. Implementing a global seismic network for real-time detection of underwater earthquakes requires applying the proposed technique to the existing extensive submarine optical fiber network.

Forgone but not forgotten: the effects of partial and full feedback in "harsh" and "kind" environments.

In a perfect world, the choice of any course of action would lead to a satisfactory outcome, and we would obtain feedback about both our chosen course and those we have chosen to forgo. In reality, however, we often face harsh environments in which we can only minimize losses, and we receive impoverished feedback. In these studies, we examined how decision makers dealt with these challenges in a simple task in which we manipulated three features of the decision: The outcomes from the available options were either mostly positive or mostly negative (kind or harsh environment); feedback was either full or partial (outcomes revealed for all options or only for the chosen option); and for the final 20 trials in a sequence, participants either chose on each trial or set an "advance-directive" policy. The propensity to choose the better option was explained by several factors: Full feedback was more beneficial in harsh than in kind environments; policy decisions encouraged better decisions and ameliorated the adverse impact of a harsh environment; and beliefs about the value of strategy diversification predicted switch rates and choice quality. The results suggest a subtle interplay between bottom-up and top-down processes: Although harsh environments encourage poor choices, and some decision makers choose less well than others, this need not imply that the decision maker has failed to identify the better option.

Using microfiber and steam technology to improve cleaning outcomes in an intensive care unit.

The use of microfiber and steam technology may be seen as a novel cleaning method that can improve the outcome of cleaning. We describe its use in an intensive care setting, its impact on vancomycin-resistant enterococci acquisition, and the importance of ensuring adequate education of cleaning staff. Such new methods can have a significant impact on the transmission of multidrug-resistant organisms, provided systems are in place to ensure that the methodology is adhered to and that cleaning hours are adequate.

Facet selectivity in gold binding peptides: exploiting interfacial water structure.

Peptide sequences that can discriminate between gold facets under aqueous conditions offer a promising route to control the growth and organisation of biomimetically-synthesised gold nanoparticles. Knowledge of the interplay between sequence, conformations and interfacial properties is essential for predictable manipulation of these biointerfaces, but the structural connections between a given peptide sequence and its binding affinity remain unclear, impeding practical advances in the field. These structural insights, at atomic-scale resolution, are not easily accessed with experimental approaches, but can be delivered via molecular simulation. A current unmet challenge lies in forging links between predicted adsorption free energies derived from enhanced sampling simulations with the conformational ensemble of the peptide and the water structure at the surface. To meet this challenge, here we use an in situ combination of Replica Exchange with Solute Tempering with Metadynamics simulations to predict the adsorption free energy of a gold-binding peptide sequence, AuBP1, at the aqueous Au(111), Au(100)(1 × 1) and Au(100)(5 × 1) interfaces. We find adsorption to the Au(111) surface is stronger than to Au(100), irrespective of the reconstruction status of the latter. Our predicted free energies agree with experiment, and correlate with trends in interfacial water structuring. For gold, surface hydration is predicted as a chief determining factor in peptide-surface recognition. Our findings can be used to suggest how shaped seed-nanocrystals of Au, in partnership with AuBP1, could be used to control AuNP nanoparticle morphology.

Structure and properties of citrate overlayers adsorbed at the aqueous Au(111) interface.

One of the most common means of gold nanoparticle (AuNP) biofunctionalization involves the manipulation of precursor citrate-capped AuNPs via ligand displacement. However, the molecular-level structural characteristics of the citrate overlayer adsorbed at the aqueous Au interface at neutral pH remain largely unknown. Access to atomistic-scale details of these interfaces will contribute much needed insight into how AuNPs can be manipulated and exploited in aqueous solution. Here, the structures of such citrate overlayers adsorbed at the aqueous Au(111) interface at pH 7 are predicted and characterized using atomistic molecular dynamics simulations, for a range of citrate surface densities. We find that the overlayers are disordered in the surface density range considered, and that many of their key characteristics are invariant with surface density. In particular, we predict the overlayers to have 3-D, rather than 2-D, morphologies, with the anions closest to the gold surface being oriented with their carboxylate groups pointing away from the surface. We predict both striped and island morphologies for our overlayers, depending on the citrate surface density, and in all cases we find bare patches of the gold surface are present. Our simulations suggest that both citrate-gold adsorption and citrate-counterion pairing contribute to the stability of these citrate overlayer morphologies. We also calculate the free energy of adsorption at the aqueous Au(111) interface of a single citrate molecule, and compare this with the corresponding value for a single arginine molecule. These findings enable us to predict the conditions under which ligand displacement of surface-adsorbed citrate by arginine may take place. Our findings represent the first steps toward elucidating a more elaborate, detailed atomistic-scale model relating to the biofunctionalization of citrate-capped AuNPs.

Structure of arginine overlayers at the aqueous gold interface: implications for nanoparticle assembly.

Adsorption of small biomolecules onto the surface of nanoparticles offers a novel route to generation of nanoparticle assemblies with predictable architectures. Previously, ligand-exchange experiments on citrate-capped gold nanoparticles with the amino acid arginine were reported to support linear nanoparticle assemblies. Here, we use a combination of atomistic modeling with experimental characterization to explore aspects of the assembly hypothesis for these systems. Using molecular simulation, we probe the structural and energetic characteristics of arginine overlayers on the Au(111) surface under aqueous conditions at both low- and high-coverage regimes. In the low-density regime, the arginines lie flat on the surface. At constant composition, these overlayers are found to be lower in energy than the densely packed films, although the latter case appears kinetically stable when arginine is adsorbed via the zwitterion group, exposing the charged guanidinium group to the solvent. Our findings suggest that zwitterion-zwitterion hydrogen bonding at the gold surface and minimization of the electrostatic repulsion between adjacent guanidinium groups play key roles in determining arginine overlayer stability at the aqueous gold interface. Ligand-exchange experiments of citrate-capped gold nanoparticles with arginine derivatives agmatine and N-methyl-l-arginine reveal that modification at the guanidinium group significantly diminishes the propensity for linear assembly of the nanoparticles.

Biomolecular adsorption at aqueous silver interfaces: first-principles calculations, polarizable force-field simulations, and comparisons with gold.

The molecular simulation of biomolecules adsorbed at noble metal interfaces can assist in the development of bionanotechnology applications. In line with advances in polarizable force fields for adsorption at aqueous gold interfaces, there is scope for developing a similar force field for silver. One way to accomplish this is via the generation of in vacuo adsorption energies calculated using first-principles approaches for a wide range of different but biologically relevant small molecules, including water. Here, we present such first-principles data for a comprehensive range of bio-organic molecules obtained from plane-wave density functional theory calculations using the vdW-DF functional. As reported previously for the gold force field, GolP-CHARMM (Wright, L. B.; Rodger, P. M.; Corni, S.; Walsh, T. R. GolP-CHARMM: first-principles based force-fields for the interaction of proteins with Au(111) and Au(100). J. Chem. Theory Comput. 2013, 9, 1616-1630), we have used these data to construct a a new force field, AgP-CHARMM, suitable for the simulation of biomolecules at the aqueous Ag(111) and Ag(100) interfaces. This force field is derived to be consistent with GolP-CHARMM such that adsorption on Ag and Au can be compared on an equal footing. Our force fields are used to evaluate the water overlayer stability on both silver and gold, finding good agreement with known behaviors. We also calculate and compare the structuring (spatial and orientational) of liquid water adsorbed at both silver and gold. Finally, we report the adsorption free energy of a range of amino acids at both the Au(111) and Ag(111) aqueous interfaces, calculated using metadynamics. Stronger adsorption on gold was noted in most cases, with the exception being the carboxylate group present in aspartic acid. Our findings also indicate differences in the binding free energy profile between silver and gold for some amino acids, notably for His and Arg. Our analysis suggests that the relatively stronger structuring of the first water layer on silver, relative to gold, could give rise to these differences.

"Down the drain": carbapenem-resistant bacteria in intensive care unit patients and handwashing sinks.

OBJECTIVES: Clinical utility of carbapenem antibiotics is under threat because of the emergence of acquired metallo-ß-lactamase (MBL) genes. We describe an outbreak in an intensive care unit (ICU) possibly associated with contaminated sinks. DESIGN, SETTING AND PARTICIPANTS: Four clusters of gram-negative bacteria harbouring the MBL gene blaIMP-4 were detected in the ICU at Dandenong Hospital between November 2009 and July 2012. Epidemiological investigations were undertaken in order to identify a common point source. During September 2012, screening using rectal swabs for all ICU patients, and environmental swabs targeting all ICU handwashing sinks and taps were collected. Samples were cultured onto selective carbapenem-resistant Enterobacteriaceae (CRE) agar. Suspected CRE isolates were further characterised using the modified Hodge test and VITEK 2 and confirmed by polymerase chain reaction and sequencing of MBL genes. Clinical and environmental CRE isolates were typed by pulsed-field gel electrophoresis. RESULTS: Ten clinical isolates and one screening isolate of CRE (consisting of Klebsiella pneumoniae [5], Serratia marcescens [4], Enterobacter cloacae [1] and Escherichia coli [1]) were detected with the blaIMP-4 gene over the 30-03 period. S. marcescens was isolated persistently from the grating and drain of eight central sinks. Molecular typing confirmed that clinical and environmental isolates were related. Tap water cultures were negative. Several attempts to clean and decontaminate the sinks using detergents and steam cleaning proved unsuccessful. CONCLUSION: This report highlights the importance of identification of potential environmental reservoirs, such as sinks, for control of outbreaks of environmentally hardy multiresistant organisms.

Efficient conformational sampling of peptides adsorbed onto inorganic surfaces: insights from a quartz binding peptide.

Harnessing the properties of biomolecules, such as peptides, adsorbed on inorganic surfaces is of interest to many cross-disciplinary areas of science, ranging from biomineralisation to nanomedicine. Key to advancing research in this area is determination of the peptide conformation(s) in its adsorbed state, at the aqueous interface. Molecular simulation is one such approach for accomplishing this goal. In this respect, use of temperature-based replica-exchange molecular dynamics (T-REMD) can yield enhanced sampling of the interfacial conformations, but does so at great computational expense, chiefly because of the need to include an explicit representation of water at the interface. Here, we investigate a number of more economical variations on REMD, chiefly those based on Replica Exchange with Solvent Tempering (REST), using the aqueous quartz-binding peptide S1-(100) α-quartz interfacial system as a benchmark. We also incorporate additional implementation details specifically targeted at improving sampling of biomolecules at interfaces. We find the REST-based variants yield configurational sampling of the peptide-surface system comparable with T-REMD, at a fraction of the computational time and resource. Our findings also deliver novel insights into the binding behaviour of the S1 peptide at the quartz (100) surface that are consistent with available experimental data.

Improving antibiotic stewardship by involving nurses.

Antimicrobial stewardship programs are important preventative strategies to reduce hospital-acquired infection, typically involving medical and pharmacy staff. Because nurses are pivotal in administering medication prescribed by medical staff and filled by pharmacy staff, we assessed nursing attitudes and antimicrobial stewardship knowledge before and after an education intervention that focused on nursing involvement in antimicrobial management. This study supports involving nurses as a means of improving antibiotic stewardship.

GolP-CHARMM: First-Principles Based Force Fields for the Interaction of Proteins with Au(111) and Au(100).

Computational simulation of peptide adsorption at the aqueous gold interface is key to advancing the development of many applications based on gold nanoparticles, ranging from nanomedical devices to smart biomimetic materials. Here, we present a force field, GolP-CHARMM, designed to capture peptide adsorption at both the aqueous Au(111) and Au(100) interfaces. The force field, compatible with the bio-organic force field CHARMM, is parametrized using a combination of experimental and first-principles data. Like its predecessor, GolP (Iori, F.; et al. J. Comput. Chem.2009, 30, 1465), this force field contains terms to describe the dynamic polarization of gold atoms, chemisorbing species, and the interaction between sp(2) hybridized carbon atoms and gold. A systematic study of small molecule adsorption at both surfaces using the vdW-DF functional (Dion, M.; et al. Phys. Rev. Lett.2004, 92, 246401-1. Thonhauser, T.; et al. Phys. Rev. B2007, 76, 125112) is carried out to fit and test force field parameters and also, for the first time, gives unique insights into facet selectivity of gold binding in vacuo. Energetic and spatial trends observed in our DFT calculations are reproduced by the force field under the same conditions. Finally, we use the new force field to calculate adsorption energies, under aqueous conditions, for a representative set of amino acids. These data are found to agree with experimental findings.

First-principles molecular dynamics simulations of NH4(+) and CH3COO(-) adsorption at the aqueous quartz interface.

The ability to exert molecular-level control at the aqueous interface between biomolecules and inorganic substrates is pivotal to advancing applications ranging from sustainable manufacturing to targeted therapeutics. Progress is hindered by a lack of structural information of these interfaces with atomic resolution. Molecular simulation is one approach to obtain such data, but can be limited by the reliability of the force-field used. First-principles simulations, in principle, can provide insights into such aqueous interfaces, but are resource-intensive, limiting previous first-principles studies to approximate the environment of liquid water. Here, we use Car-Parrinello simulations to investigate adsorption of two charged adsorbates that are functional groups common to all amino-acids--ethanoate and ammonium--at the interface between hydroxylated quartz and liquid water, directly incorporating full solvation effects at the interface. Our findings reveal the stable character of carboxylate-quartz binding, as well as the surprisingly indifferent nature of ammonium-quartz interactions, in liquid water.

Prediction of acoustic radiation from axisymmetric surfaces with arbitrary boundary conditions using the boundary element method on a distributed computing system.

This paper presents a computational technique using the boundary element method for prediction of radiated acoustic waves from axisymmetric surfaces with nonaxisymmetric boundary conditions. The aim is to predict the far-field behavior of underwater acoustic transducers based on their measured behavior in the near-field. The technique is valid for all wavenumbers and uses a volume integral method to calculate the singular integrals required by the boundary element formulation. The technique has been implemented on a distributed computing system to take advantage of its parallel nature, which has led to significant reductions in the time required to generate results. Measurement data generated by a pair of free-flooding underwater acoustic transducers encapsulated in a polyurethane polymer have been used to validate the technique against experiment. The dimensions of the outer surface of the transducers (including the polymer coating) were an outer diameter of 98 mm with an 18 mm wall thickness and a length of 92 mm. The transducers were mounted coaxially, giving an overall length of 185 mm. The cylinders had resonance frequencies at 13.9 and 27.5 kHz, and the data were gathered at these frequencies.