Opportunities for system level improvement in antibiotic use across the surgical pathway

Optimizing antibiotic prescribing across the surgical pathway (before, during, and after surgery) is a key aspect of tackling important drivers of antimicrobial resistance and simultaneously decreasing the burden of infection at the global level. In the UK alone, 10 million patients undergo surgery every year, which is equivalent to 60% of the annual hospital admissions having a surgical intervention. The overwhelming majority of surgical procedures require effectively limited delivery of antibiotic prophylaxis to prevent infections. Evidence from around the world indicates that antibiotics for surgical prophylaxis are administered ineffectively, or are extended for an inappropriate duration of time postoperatively. Ineffective antibiotic prophylaxis can contribute to the development of surgical site infections (SSIs), which represent a significant global burden of disease. The World Health Organization estimates SSI rates of up to 50% in postoperative surgical patients (depending on the type of surgery), with a particular problem in low- and middle-income countries, where SSIs are the most frequently reported healthcare-associated infections. Across European hospitals, SSIs alone comprise 19.6% of all healthcare-acquired infections. Much of the scientific research in infection management in surgery is related to infection prevention and control in the operating room, surgical prophylaxis, and the management of SSIs, with many studies focusing on infection within the 30-day postoperative period. However it is important to note that SSIs represent only one of the many types of infection that can occur postoperatively. This article provides an overview of the surgical pathway and considers infection management and antibiotic prescribing at each step of the pathway. The aim was to identify the implications for research and opportunities for system improvement

Point-of-Care Diagnostics for Infection and Antimicrobial Resistance in Sub-Saharan Africa - A Narrative Review.

INTRODUCTION Sub-Saharan African (SSA) countries are severely impacted by antimicrobial resistance (AMR). Due to gaps in access to diagnostics in SSA the true extent of AMR remains unknown. This diagnostic gap affects patient management and leads to significant antimicrobial overuse. This review explores how point-of-care (POC) testing for pathogen identification and AMR may be used to close the diagnostic gap in SSA countries. METHODS A narrative review exploring current clinical practice and novel developments in the field of point-of-care (POC) testing for infectious diseases and AMR. FINDINGS POC assays for identification of various pathogens have been successfully rolled out in SSA countries. While implementation studies have mostly highlighted impressive test performance of POC assays, there is limited data on effect of implementation on clinical outcomes and cost-effectiveness. We did not encounter local studies of host-directed POC assays relevant to AMR. Novel POC assays using real-time PCR, isothermal amplification, microfluidics and other technologies are in various stages of development. DISCUSSION Available literature shows that POC testing for AMR applications is implementable in SSA and holds the potential to reduce the diagnostic gap. Implementation will require effective regulatory pathways, incorporation of POC testing in clinical and laboratory guidelines, and adequate value capture in existing health financing models

Twirling Elastica: Kinks, Viscous Drag, and Torsional Stress

Biological filaments such as DNA or bacterial flagella are typically curved in their natural states. To elucidate the interplay of viscous drag, twisting, and bending in the overdamped dynamics of such filaments, we compute the steady-state torsional stress and shape of a rotating rod with a kink. Drag deforms the rod, ultimately extending or folding it depending on the kink angle. For certain kink angles and kink locations, both states are possible at high rotation rates. The agreement between our macroscopic experiments and the theory is good, with no adjustable parameters.Comment: 4 pages, 4 figure

The Viscous Nonlinear Dynamics of Twist and Writhe

Exploiting the "natural" frame of space curves, we formulate an intrinsic dynamics of twisted elastic filaments in viscous fluids. A pair of coupled nonlinear equations describing the temporal evolution of the filament's complex curvature and twist density embodies the dynamic interplay of twist and writhe. These are used to illustrate a novel nonlinear phenomenon: ``geometric untwisting" of open filaments, whereby twisting strains relax through a transient writhing instability without performing axial rotation. This may explain certain experimentally observed motions of fibers of the bacterium B. subtilis [N.H. Mendelson, et al., J. Bacteriol. 177, 7060 (1995)].Comment: 9 pages, 4 figure

A Paraconsistent Higher Order Logic

Classical logic predicts that everything (thus nothing useful at all) follows from inconsistency. A paraconsistent logic is a logic where an inconsistency does not lead to such an explosion, and since in practice consistency is difficult to achieve there are many potential applications of paraconsistent logics in knowledge-based systems, logical semantics of natural language, etc. Higher order logics have the advantages of being expressive and with several automated theorem provers available. Also the type system can be helpful. We present a concise description of a paraconsistent higher order logic with countable infinite indeterminacy, where each basic formula can get its own indeterminate truth value (or as we prefer: truth code). The meaning of the logical operators is new and rather different from traditional many-valued logics as well as from logics based on bilattices. The adequacy of the logic is examined by a case study in the domain of medicine. Thus we try to build a bridge between the HOL and MVL communities. A sequent calculus is proposed based on recent work by Muskens.Comment: Originally in the proceedings of PCL 2002, editors Hendrik Decker, Joergen Villadsen, Toshiharu Waragai (http://floc02.diku.dk/PCL/). Correcte

Gravitational Microlensing Evidence for a Planet Orbiting a Binary Star System

The study of extra-solar planetary systems has emerged as a new discipline of observational astronomy in the past few years with the discovery of a number of extra-solar planets. The properties of most of these extra-solar planets were not anticipated by theoretical work on the formation of planetary systems. Here we report observations and light curve modeling of gravitational microlensing event MACHO-97-BLG-41, which indicates that the lens system consists of a planet orbiting a binary star system. According to this model, the mass ratio of the binary star system is 3.8:1 and the stars are most likely to be a late K dwarf and an M dwarf with a separation of about 1.8 AU. A planet of about 3 Jupiter masses orbits this system at a distance of about 7 AU. If our interpretation of this light curve is correct, it represents the first discovery of a planet orbiting a binary star system and the first detection of a Jovian planet via the gravitational microlensing technique. It suggests that giant planets may be common in short period binary star systems.Comment: 11 pages, with 1 color and 2 b/w Figures included (published version

Semiflexible chains in confined spaces

We develop an analytical method for studying the properties of a noninteracting wormlike chain (WLC) in confined geometries. The mean-field-like theory replaces the rigid constraints of confinement with average constraints, thus allowing us to develop a tractable method for treating a WLC wrapped on the surface of a sphere, and fully encapsulated within it. The efficacy of the theory is established by reproducing the exact correlation functions for a WLC confined to the surface of a sphere. In addition, the coefficients in the free energy are exactly calculated. We also describe the behavior of a surface-confined chain under external tension that is relevant for single molecule experiments on histone-DNA complexes. The force-extension curves display spatial oscillations, and the extension of the chain, whose maximum value is bounded by the sphere diameter, scales as f−1 at large forces, in contrast to the unconfined chain that approaches the contour length as f−1∕2. A WLC encapsulated in a sphere, that is relevant for the study of the viral encapsulation of DNA, can also be treated using the mean-field approach. The predictions of the theory for various correlation functions are in excellent agreement with Langevin simulations. We find that strongly confined chains are highly structured by examining the correlations using a local winding axis. The predicted pressure of the system is in excellent agreement with simulations but, as is known, is significantly lower than the pressures seen for DNA packaged in viral capsids

Twirling and Whirling: Viscous Dynamics of Rotating Elastica

Motivated by diverse phenomena in cellular biophysics, including bacterial flagellar motion and DNA transcription and replication, we study the overdamped nonlinear dynamics of a rotationally forced filament with twist and bend elasticity. Competition between twist injection, twist diffusion, and writhing instabilities is described by a novel pair of coupled PDEs for twist and bend evolution. Analytical and numerical methods elucidate the twist/bend coupling and reveal two dynamical regimes separated by a Hopf bifurcation: (i) diffusion-dominated axial rotation, or twirling, and (ii) steady-state crankshafting motion, or whirling. The consequences of these phenomena for self-propulsion are investigated, and experimental tests proposed.Comment: To be published in Physical Review Letter

Labels for non-individuals

Quasi-set theory is a first order theory without identity, which allows us to cope with non-individuals in a sense. A weaker equivalence relation called ``indistinguishability'' is an extension of identity in the sense that if $x$ is identical to $y$ then $x$ and $y$ are indistinguishable, although the reciprocal is not always valid. The interesting point is that quasi-set theory provides us a useful mathematical background for dealing with collections of indistinguishable elementary quantum particles. In the present paper, however, we show that even in quasi-set theory it is possible to label objects that are considered as non-individuals. We intend to prove that individuality has nothing to do with any labelling process at all, as suggested by some authors. We discuss the physical interpretation of our results.Comment: 11 pages, no figure

Signs of low frequency dispersions in disordered binary dielectric mixtures (50-50)

Dielectric relaxation in disordered dielectric mixtures are presented by emphasizing the interfacial polarization. The obtained results coincide with and cause confusion with those of the low frequency dispersion behavior. The considered systems are composed of two phases on two-dimensional square and triangular topological networks. We use the finite element method to calculate the effective dielectric permittivities of randomly generated structures. The dielectric relaxation phenomena together with the dielectric permittivity values at constant frequencies are investigated, and significant differences of the square and triangular topologies are observed. The frequency dependent properties of some of the generated structures are examined. We conclude that the topological disorder may lead to the normal or anomalous low frequency dispersion if the electrical properties of the phases are chosen properly, such that for ``slightly'' {\em reciprocal mixture}--when $\sigma_1\gg\sigma_2$, and $\epsilon_1<\epsilon_2$--normal, and while for ``extreme'' {\em reciprocal mixture}--when $\sigma_1\gg\sigma_2$, and $\epsilon_1\ll\epsilon_2$--anomalous low frequency dispersions are obtained. Finally, comparison with experimental data indicates that one can obtain valuable information from simulations when the material properties of the constituents are not available and of importance.Comment: 13 pages, 7 figure