Implementation and impact of pediatric antimicrobial stewardship programs: a systematic scoping review.

Background: Antibiotics are the most common medicines prescribed to children in hospitals and the community, with a high proportion of potentially inappropriate use. Antibiotic misuse increases the risk of toxicity, raises healthcare costs, and selection of resistance. The primary aim of this systematic review is to summarize the current state of evidence of the implementation and outcomes of pediatric antimicrobial stewardship programs (ASPs) globally. Methods: MEDLINE, Embase and Cochrane Library databases were systematically searched to identify studies reporting on ASP in children aged 0-18 years and conducted in outpatient or in-hospital settings. Three investigators independently reviewed identified articles for inclusion and extracted relevant data. Results: Of the 41,916 studies screened, 113 were eligible for inclusion in this study. Most of the studies originated in the USA (52.2%), while a minority were conducted in Europe (24.7%) or Asia (17.7%). Seventy-four (65.5%) studies used a before-and-after design, and sixteen (14.1%) were randomized trials. The majority (81.4%) described in-hospital ASPs with half of interventions in mixed pediatric wards and ten (8.8%) in emergency departments. Only sixteen (14.1%) studies focused on the costs of ASPs. Almost all the studies (79.6%) showed a significant reduction in inappropriate prescriptions. Compliance after ASP implementation increased. Sixteen of the included studies quantified cost savings related to the intervention with most of the decreases due to lower rates of drug administration. Seven studies showed an increased susceptibility of the bacteria analysed with a decrease in extended spectrum beta-lactamase producers E. coli and K. pneumoniae; a reduction in the rate of P. aeruginosa carbapenem resistance subsequent to an observed reduction in the rate of antimicrobial days of therapy; and, in two studies set in outpatient setting, an increase in erythromycin-sensitive S. pyogenes following a reduction in the use of macrolides. Conclusions: Pediatric ASPs have a significant impact on the reduction of targeted and empiric antibiotic use, healthcare costs, and antimicrobial resistance in both inpatient and outpatient settings. Pediatric ASPs are now widely implemented in the USA, but considerable further adaptation is required to facilitate their uptake in Europe, Asia, Latin America and Africa

Metastatic uveal melanoma managed with best supportive care

Non peer reviewe

Poisson equation and self-consistent periodical Anderson model

We show that the formally exact expression for the free energy (with a non-relativistic Hamiltonian) for the correlated metal generates the Poisson equation within the saddle-point approximation for the electric potential, where the charge density automatically includes correlations. In this approximation the problem is reduced to the self-consistent periodical Anderson model (SCPAM). The parameter of the mixing interaction in this formulation have to be found self-consistently together with the correlated charge density. The factors, calculated by Irkhin, for the mixing interaction, which reflect the structure of the many-electron states of the \f-ion involved, arise automatically in this formulation and are quite sensitive to the specific element we are interested in. We also discuss the definitions of the mixing interaction for the mapping from ab initio to model calculations.Comment: 25 pages, no figure

Methyl methanesulfonate (MMS) produces heat-labile DNA damage but no detectable in vivo DNA double-strand breaks

Homologous recombination (HR) deficient cells are sensitive to methyl methanesulfonate (MMS). HR is usually involved in the repair of DNA double-strand breaks (DSBs) in Saccharomyces cerevisiae implying that MMS somehow induces DSBs in vivo. Indeed there is evidence, based on pulsed-field gel electrophoresis (PFGE), that MMS causes DNA fragmentation. However, the mechanism through which MMS induces DSBs has not been demonstrated. Here, we show that DNA fragmentation following MMS treatment, and detected by PFGE is not the consequence of production of cellular DSBs. Instead, DSBs seen following MMS treatment are produced during sample preparation where heat-labile methylated DNA is converted into DSBs. Furthermore, we show that the repair of MMS-induced heat-labile damage requires the base excision repair protein XRCC1, and is independent of HR in both S.cerevisiae and mammalian cells. We speculate that the reason for recombination-deficient cells being sensitive to MMS is due to the role of HR in repair of MMS-induced stalled replication forks, rather than for repair of cellular DSBs or heat-labile damage

The dual nature of 5f electrons and origin of heavy fermions in U compounds

We develop a theory for the electronic excitations in UPt$_3$ which is based on the localization of two of the $5f$ electrons. The remaining $f$ electron is delocalized and acquires a large effective mass by inducing intra-atomic excitations of the localized ones. The measured deHaas-vanAlphen frequencies of the heavy quasiparticles are explained as well as their anisotropic heavy mass. A model calculation for a small cluster reveals why only the largest of the different $5f$ hopping matrix elements is operative causing the electrons in other orbitals to localize.Comment: 6 pages, 3 figure

Target ion and neutral spread in high power impulse magnetron sputtering

In magnetron sputtering, only a fraction of the sputtered target material leaving the ionization region is directed toward the substrate. This fraction may be different for ions and neutrals of the target material as the neutrals and ions can exhibit a different spread as they travel from the target surface toward the substrate. This difference can be significant in high power impulse magnetron sputtering (HiPIMS) where a substantial fraction of the sputtered material is known to be ionized. Geometrical factors or transport parameters that account for the loss of produced film-forming species to the chamber walls are needed for experimental characterization and modeling of the magnetron sputtering discharge. Here, we experimentally determine transport parameters for ions and neutral atoms in a HiPIMS discharge with a titanium target for various magnet configurations. Transport parameters are determined to a typical substrate, with the same diameter (100 mm) as the cathode target, and located at a distance 70 mm from the target surface. As the magnet configuration and/or the discharge current are changed, the transport parameter for neutral atoms ζ tn remains roughly the same, while transport parameters for ions ζ ti vary greatly. Furthermore, the relative ion-to-neutral transport factors, ζ ti / ζ tn, that describe the relative deposited fractions of target material ions and neutrals onto the substrate, are determined to be in the range from 0.4 to 1.1

Temperature dependence of polaronic transport through single molecules and quantum dots

Motivated by recent experiments on electric transport through single molecules and quantum dots, we investigate a model for transport that allows for significant coupling between the electrons and a boson mode isolated on the molecule or dot. We focus our attention on the temperature dependent properties of the transport. In the Holstein picture for polaronic transport in molecular crystals the temperature dependence of the conductivity exhibits a crossover from coherent (band) to incoherent (hopping) transport. Here, the temperature dependence of the differential conductance on resonance does not show such a crossover, but is mostly determined by the lifetime of the resonant level on the molecule or dot.Comment: 8 pages, 7 figure

On the electron energy distribution function in the high power impulse magnetron sputtering discharge

We apply the Ionization Region Model (IRM) and the Orsay Boltzmann equation for ELectrons coupled with Ionization and eXcited states kinetics (OBELIX) model to study the electron kinetics of a high power impulse magnetron sputtering (HiPIMS) discharge. In the IRM the bulk (cold) electrons are assumed to exhibit a Maxwellian energy distribution and the secondary (hot) electrons, emitted from the target surface upon ion bombardment, are treated as a high energy tail, while in the OBELIX the electron energy distribution is calculated self-consistently using an isotropic Boltzmann equation. The two models are merged in the sense that the output from the IRM is used as an input for OBELIX. The temporal evolutions of the particle densities are found to agree very well between the two models. Furthermore, a very good agreement is demonstrated between the bi-Maxwellian electron energy distribution assumed by the IRM and the electron energy distribution calculated by the OBELIX model. It can therefore be concluded that assuming a bi-Maxwellian electron energy distribution, constituting a cold bulk electron group and a hot secondary electron group, is a good approximation for modeling the HiPIMS discharge

Periodic Anderson model with degenerate orbitals: linearized dynamical mean field theory approach

We investigate a multi-orbital extension of the periodic Anderson model with particular emphasis on electron correlations including orbital fluctuations. By means of a linearized version of the dynamical mean-field theory, we compute the renormalization factor, the density of states, the spectral gap and the local correlation functions for a given set of the intra- and inter-orbital Coulomb interactions as well as the Hund coupling. It is found that when a certain condition is met for the intra- and inter-orbital interactions for $f$ electrons, orbital fluctuations are enhanced, thereby enlarging the Kondo insulating gap. This effect is suppressed in the presence of the Hund coupling. We also clarify how the Kondo insulator is continuously changed to the Mott insulator when electron correlations among conduction electrons are increased.Comment: 7 pages, 10 figure

Linking Whole-Slide Microscope Images with DICOM by Using JPEG2000 Interactive Protocol

The use of digitized histopathologic specimens (also known as whole-slide images (WSIs)) in clinical medicine requires compatibility with the Digital Imaging and Communications in Medicine (DICOM) standard. Unfortunately, WSIs usually exceed DICOM image object size limit, making it impossible to store and exchange them in a straightforward way. Moreover, transmitting the entire DICOM image for viewing is ineffective for WSIs. With the JPEG2000 Interactive Protocol (JPIP), WSIs can be linked with DICOM by transmitting image data over an auxiliary connection, apart from patient data. In this study, we explored the feasibility of using JPIP to link JPEG2000 WSIs with a DICOM-based Picture Archiving and Communications System (PACS). We first modified an open-source DICOM library by adding support for JPIP as described in the existing DICOM Supplement 106. Second, the modified library was used as a basis for a software package (JVSdicom), which provides a proof-of-concept for a DICOM client–server system that can transmit patient data, conventional DICOM imagery (e.g., radiological), and JPIP-linked JPEG2000 WSIs. The software package consists of a compression application (JVSdicom Compressor) for producing DICOM-compatible JPEG2000 WSIs, a DICOM PACS server application (JVSdicom Server), and a DICOM PACS client application (JVSdicom Workstation). JVSdicom is available for free from our Web site (http://jvsmicroscope.uta.fi/), which also features a public JVSdicom Server, containing example X-ray images and histopathology WSIs of breast cancer cases. The software developed indicates that JPEG2000 and JPIP provide a well-working solution for linking WSIs with DICOM, requiring only minor modifications to current DICOM standard specification