Antimicrobials: a global alliance for optimizing their rational use in intra-abdominal infections (AGORA)

Intra-abdominal infections (IAI) are an important cause of morbidity and are frequently associated with poor prognosis, particularly in high-risk patients. The cornerstones in the management of complicated IAIs are timely effective source control with appropriate antimicrobial therapy. Empiric antimicrobial therapy is important in the management of intra-abdominal infections and must be broad enough to cover all likely organisms because inappropriate initial antimicrobial therapy is associated with poor patient outcomes and the development of bacterial resistance. The overuse of antimicrobials is widely accepted as a major driver of some emerging infections (such as C. difficile), the selection of resistant pathogens in individual patients, and for the continued development of antimicrobial resistance globally. The growing emergence of multi-drug resistant organisms and the limited development of new agents available to counteract them have caused an impending crisis with alarming implications, especially with regards to Gram-negative bacteria. An international task force from 79 different countries has joined this project by sharing a document on the rational use of antimicrobials for patients with IAIs. The project has been termed AGORA (Antimicrobials: A Global Alliance for Optimizing their Rational Use in Intra-Abdominal Infections). The authors hope that AGORA, involving many of the world's leading experts, can actively raise awareness in health workers and can improve prescribing behavior in treating IAIs

Active Transport of Peptides Across the Intact Human Tympanic Membrane.

We previously identified peptides that are actively transported across the intact tympanic membrane (TM) of rats with infected middle ears. To assess the possibility that this transport would also occur across the human TM, we first developed and validated an assay to evaluate transport in vitro using fragments of the TM. Using this assay, we demonstrated the ability of phage bearing a TM-transiting peptide to cross freshly dissected TM fragments from infected rats or from uninfected rats, guinea pigs and rabbits. We then evaluated transport across fragments of the human TM that were discarded during otologic surgery. Human trans-TM transport was similar to that seen in the animal species. Finally, we found that free peptide, unconnected to phage, was transported across the TM at a rate comparable to that seen for peptide-bearing phage. These studies provide evidence supporting the concept of peptide-mediated drug delivery across the intact TM and into the middle ears of patients

Trajectory mapping: A tool for validation of trace gas observations

We investigate the effectiveness of trajectory mapping(TM) as a data validation tool. TM combines a dynamical model of the atmosphere with trace gas observations to provide more statistically robust estimates of instrument performance over much broader geographic areas than traditional techniques are able to provide. We present four detailed case studies selected so that the traditional techniques are expected to work well. In each case the TM results are equivalent to or improve upon the measurement comparisons performed with traditional approaches. The TM results are statistically more robust than those achieved using traditional approaches since the TM comparisons occur over a much larger range of geophysical variability. In the first case study we compare ozone data from the Halogen Occultation Experiment (HALOE) with Microwave Limb Sounder(MLS). TM comparisons appear to introduce little to no error as compared to the traditional approach. In the second case study we compare ozone data from HALOE with that from the Stratospheric Aerosol and Gas Experiment TT(SAGE TT). TM results in differences of less than 5% as compared to the traditional approach at altitudes between 18 and 25 km and less than 10% at altitudes between 25 and 40 km.In the third case study we show that ozone profiles generated from HALOE data using TM compare well with profiles from five European ozonesondes. In the fourth case study we evaluate the precision of MLS H20 using TM and find typical precision uncertainties of 3-7% at most latitudes and altitudes. The TM results agree well with previous estimates but are the result of a global analysis of the data rather than an analysis in the limited latitude bands in which traditional approaches work. Finally, sensitivity studies using the MLS H20 data show the following: (1) a combination of forward and backward trajectory calculations minimize uncertainties in isentropic TM; (2) although the uncertainty of the technique increases with trajectory duration,TM calculations of up to 14 days can provide reliable information for use in data validation studies; (3) a correlation coincidence criterion of 400 km produces the best TM results under most circumstances; (4) TM performs well compared to (and sometimes better than) traditional approaches at all latitudes and in most seasons and; (5) TM introduces no statistically significant biases at altitudes between 22 and 40 km

First-order transitions in glasses and melts induced by solid superclusters nucleated and melted by homogeneous nucleation instead of surface melting

Supercooled liquids give rise, by homogeneous nucleation, to solid superclusters acting as building blocks of glass, ultrastable glass, and glacial glass phases before being crystallized. Liquid-to-liquid phase transitions begin to be observed above the melting temperature Tm as well as critical undercooling depending on critical overheating (Tm-T)/Tm. Solid nuclei exist above Tm and melt by homogeneous nucleation of liquid instead of surface melting. The Gibbs free energy change predicted by the classical nucleation equation is completed by an additional enthalpy which stabilize these solid entities during undercooling. A two-liquid model, using this renewed equation, predicts the new homogeneous nucleation temperatures inducing first-order transitions, and the enthalpy and entropy of new liquid and glass phases. These calculations are successfully applied to ethylbenzene, triphenyl phosphite, d-mannitol, n-butanol, Zr41.2Ti13.8Cu12.5Ni10Be22.5, Ti34Zr11Cu47Ni8, and Co81.5B18.5. A critical supercooling and overheating rate (Tm-T)/Tm = 0.198 of liquid elements is predicted in agreement with experiments on Sn droplets.Comment: 41 pages, 21 figures, submitted to "chemical physics

Positive scalar curvature on foliations: the noncompact case

Let $(M,g^{TM})$ be a noncompact enlargeable Riemannian manifold in the sense of Gromov-Lawson and $F$ an integrable subbundle of $TM$. Let $k^{F}$ be the leafwise scalar curvature associated to $g^F=g^{TM}|_F$. We show that if either $TM$ or $F$ is spin, then ${\rm inf}(k^F)\leq 0$. This generalizes earlier claims for hyper-Euclidean spaces made by Gromov.Comment: 14 page

Tunable temperature induced magnetization jump in a GdVO3 single crystal

We report a novel feature of the temperature induced magnetization jump observed along the a-axis of the GdVO3 single crystal at temperature TM = 0.8 K. Below TM, the compound shows no coercivity and remanent magnetization indicating a homogenous antiferromagnetic structure. However, we will demonstrate that the magnetic state below TM is indeed history dependent and it shows up in different jumps in the magnetization only when warming the sample through TM. Such a magnetic memory effect is highly unusual and suggesting different domain arrangements in the supposedly homogenous antiferromagnetic phase of the compound.Comment: 17 pages, 8 Figure