Investigation of the impact of the NICE guidelines regarding antibiotic prophylaxis during invasive dental procedures on the incidence of infective endocarditis in England: an electronic health records study

Background Infective endocarditis is an uncommon but serious infection, where evidence for giving antibiotic prophylaxis before invasive dental procedures is inconclusive. In England, antibiotic prophylaxis was offered routinely to patients at risk of infective endocarditis until March 2008, when new guidelines aimed at reducing unnecessary antibiotic use were issued. We investigated whether changes in infective endocarditis incidence could be detected using electronic health records, assessing the impact of inclusion criteria/statistical model choice on inferences about the timing/type of any change. Methods Using national data from Hospital Episode Statistics covering 1998–2017, we modelled trends in infective endocarditis incidence using three different sets of inclusion criteria plus a range of regression models, identifying the most likely date for a change in trends if evidence for one existed. We also modelled trends in the proportions of different organism groups identified during infection episodes, using secondary diagnosis codes and data from national laboratory records. Lastly, we applied non-parametric local smoothing to visually inspect any changes in trend around the guideline change date. Results Infective endocarditis incidence increased markedly over the study (22.2–41.3 per million population in 1998 to 42.0–67.7 in 2017 depending on inclusion criteria). The most likely dates for a change in incidence trends ranged from September 2001 (uncertainty interval August 2000–May 2003) to May 2015 (March 1999–January 2016), depending on inclusion criteria and statistical model used. For the proportion of infective endocarditis cases associated with streptococci, the most likely change points ranged from October 2008 (March 2006–April 2010) to August 2015 (September 2013–November 2015), with those associated with oral streptococci decreasing in proportion after the change point. Smoothed trends showed no notable changes in trend around the guideline date. Conclusions Infective endocarditis incidence has increased rapidly in England, though we did not detect any change in trends directly following the updated guidelines for antibiotic prophylaxis, either overall or in cases associated with oral streptococci. Estimates of when changes occurred were sensitive to inclusion criteria and statistical model choice, demonstrating the need for caution in interpreting single models when using large datasets. More research is needed to explore the factors behind this increase

Hadronic Masses and Regge Trajectories

A comprehensive phenomenological analysis of experimental data and some theoretical models is presented here (for mesons) to critically discuss how Regge trajectory parameters depend on flavor. Through analytic continuation of physical trajectories (obtained from resonance data) into the space like region, we derive the suppression factor for heavy flavor production. The case of our D Regge exchange, both for D and $\Lambda_c$ production, is considered in some detail. Good agreement with data is reached confirming that indeed the slopes of heavier flavors decrease. This result suggests that the confinement potential has a substantial dependence on the quark masses. In a simple non-relativistic model, constrained to produce linear Regge trajectories, it is shown that a linear quark mass dependence is required (in the confinement part of the potential) in order for the slope to decrease in the appropriate way.Comment: 19 pages, 9 Figures, IV Table

A cAMP-binding ectoprotein in the yeast Saccharomyces cerevisiae

tides 10, 593-595

Phase Behavior of Polyelectrolyte Block Copolymers in Mixed Solvents

We have studied the phase behavior of the poly(n-butyl acrylate)-b-poly(acrylic acid) block copolymer in a mixture of two miscible solvents, water and tetrahydrofuran (THF). The techniques used to examine the different polymers, structures and phases formed in mixed solvents were static and dynamic light scattering, small-angle neutron scattering, nuclear magnetic resonance and fluorescence microscopy. By lowering the water/THF mixing ratio X, the sequence unimers, micron-sized droplets, polymeric micelles was observed. The transition between unimers and the micron-sized droplets occurred at X = 0.75, whereas the microstructuration into core-shell polymeric micelles was effective below X = 0.4. At intermediate mixing ratios, a coexistence between the micron-sized droplets and the polymeric micelles was observed. Combining the different aforementioned techniques, it was concluded that the droplet dispersion resulted from a solvent partitioning that was induced by the hydrophobic blocks. Comparison of poly(n-butyl acrylate) homopolymers and poly(n-butyl acrylate)-b-poly(acrylic acid) block copolymers suggested that the droplets were rich in THF and concentrated in copolymers and that they were stabilized by the hydrophilic poly(acrylic acid) moieties.Comment: 11 pages, 12 figures, to appear in Macromolecule

Ground State Vortex Lattice Structures in d-wave Superconductors

We show in a realistic $d_{x^{2}-y^{2}}$ symmetry gap model for a cuprate superconductor that the clean vortex lattice has discontinuous structural transitions (at and near T=0), as a function of the magnetic field $B$ along the c-axis. The transitions arise from the singular nonlocal and anisotropic susceptibility of the $d_{x^{2}-y^{2}}$ superconductor to the perturbation caused by supercurrents associated with vortices. The susceptibility, due to virtual Dirac quasiparticle-hole excitation, is calculated carefully, and leads to a ground state transition for the triangular lattice from an orientation along one of the crystal axis to one at 45$^o$ to them, i.e, along the gap zero direction. The field scale is seen to be 5 Tesla $\sim (\Delta_{0}/ta)^{2}\Phi_{0}$, where $\Delta_{0}$ is the gap maximum, $t$ is the nearest neighbour hopping, $a$ is the lattice constant, and $\Phi_{0}$ is the flux quantum. At much higher fields ($\sim 28T$) there is a discontinuous transition to a centred square structure. The source of the differences from existing calculations, and experimental observability are discussed, the latter especially in view of the very small (a few degrees $K$ per vortex) differences in the ground state energy.Comment: To be published in Phys. Rev.

Modeling the break-up of nano-particle clusters in aluminum- and magnesium-based metal matrix nano-composites

Aluminum- and magnesium-based metal matrix nano-composites with ceramic nano-reinforcements promise low weight with high durability and superior strength, desirable properties in aerospace, automobile, and other applications. However, nano-particle agglomerations lead to adverse effects on final properties: large-size clusters no longer act as dislocation anchors, but instead become defects; the resulting particle distribution will be uneven, leading to inconsistent properties. To prevent agglomeration and to break-up clusters, ultrasonic processing is used via an immersed sonotrode, or alternatively via electromagnetic vibration. A study of the interaction forces holding the nano-particles together shows that the choice of adhesion model significantly affects estimates of break-up force and that simple Stokes drag due to stirring is insufficient to break-up the clusters. The complex interaction of flow and co-joint particles under a high frequency external field (ultrasonic, electromagnetic) is addressed in detail using a discrete-element method code to demonstrate the effect of these fields on de-agglomeration

Development of FRET Assay into Quantitative and High-throughput Screening Technology Platforms for Protein–Protein Interactions

Förster resonance energy transfer (FRET) technology has been widely used in biological and biomedical research and is a very powerful tool in elucidating protein interactions in many cellular processes. Ubiquitination and SUMOylation are multi-step cascade reactions, involving multiple enzymes and protein–protein interactions. Here we report the development of dissociation constant (Kd) determination for protein–protein interaction and cell-based high-throughput screening (HTS) assay in SUMOylation cascade using FRET technology. These developments are based on steady state and high efficiency of fluorescent energy transfer between CyPet and YPet fused with SUMO1 and Ubc9, respectively. The developments in theoretical and experimental procedures for protein interaction Kd determination and cell-based HTS provide novel tools in affinity measurement and protein interaction inhibitor screening. The Kd determined by FRET between SUMO1 and Ubc9 is compatible with those determined with other traditional approaches, such as isothermal titration calorimetry (ITC) and surface plasmon resonance (SPR). The FRET-based HTS is pioneer in cell-based HTS. Both Kd determination and cell-based HTS, carried out in 384-well plate format, provide powerful tools for large-scale and high-throughput applications

CCR9-CCL25 interactions promote cisplatin resistance in breast cancer cell through Akt activation in a PI3K-dependent and FAK-independent fashion

<p>Abstract</p> <p>Background</p> <p>Chemotherapy heavily relies on apoptosis to kill breast cancer (BrCa) cells. Many breast tumors respond to chemotherapy, but cells that survive this initial response gain resistance to subsequent treatments. This leads to aggressive cell variants with an enhanced ability to migrate, invade and survive at secondary sites. Metastasis and chemoresistance are responsible for most cancer-related deaths; hence, therapies designed to minimize both are greatly needed. We have recently shown that CCR9-CCL25 interactions promote BrCa cell migration and invasion, while others have shown that this axis play important role in T cell survival. In this study we have shown potential role of CCR9-CCL25 axis in breast cancer cell survival and therapeutic efficacy of cisplatin.</p> <p>Methods</p> <p>Bromodeoxyuridine (BrdU) incorporation, Vybrant apoptosis and TUNEL assays were performed to ascertain the role of CCR9-CCL25 axis in cisplatin-induced apoptosis of BrCa cells. Fast Activated Cell-based ELISA (FACE) assay was used to quantify <it>In situ </it>activation of PI3K^p85, Akt^Ser473, GSK-3β^Ser9and FKHR^Thr24in breast cancer cells with or without cisplatin treatment in presence or absence of CCL25.</p> <p>Results</p> <p>CCR9-CCL25 axis provides survival advantage to BrCa cells and inhibits cisplatin-induced apoptosis in a PI3K-dependent and focal adhesion kinase (FAK)-independent fashion. Furthermore, CCR9-CCL25 axis activates cell-survival signals through Akt and subsequent glycogen synthase kinase-3 beta (GSK-3β) and forkhead in human rhabdomyosarcoma (FKHR) inactivation. These results show that CCR9-CCL25 axis play important role in BrCa cell survival and low chemotherapeutic efficacy of cisplatin primarily through PI3K/Akt dependent fashion.</p