External validation of the 4C mortality score among COVID-19 patients admitted to hospital in Ontario, Canada: a retrospective study.

Risk prediction scores are important tools to support clinical decision-making for patients with coronavirus disease (COVID-19). The objective of this paper was to validate the 4C mortality score, originally developed in the United Kingdom, for a Canadian population, and to examine its performance over time. We conducted an external validation study within a registry of COVID-19 positive hospital admissions in the Kitchener-Waterloo and Hamilton regions of southern Ontario between March 4, 2020 and June 13, 2021. We examined the validity of the 4C score to prognosticate in-hospital mortality using the area under the receiver operating characteristic curve (AUC) with 95% confidence intervals calculated via bootstrapping. The study included 959 individuals, of whom 224 (23.4%) died in-hospital. Median age was 72 years and 524 individuals (55%) were male. The AUC of the 4C score was 0.77, 95% confidence interval 0.79-0.87. Overall mortality rates across the pre-defined risk groups were 0% (Low), 8.0% (Intermediate), 27.2% (High), and 54.2% (Very High). Wave 1, 2 and 3 values of the AUC were 0.81 (0.76, 0.86), 0.74 (0.69, 0.80), and 0.76 (0.69, 0.83) respectively. The 4C score is a valid tool to prognosticate mortality from COVID-19 in Canadian hospitals and can be used to prioritize care and resources for patients at greatest risk of death.

Impact of Physician Navigators on productivity indicators in the ED.

OBJECTIVES: We created Physician Navigators in our ED to help improve emergency physician (EP) productivity. We aimed to quantify the effect of Physician Navigators on measures of EP productivity: patient seen per hour (Pt/hr), and turn-around time (TAT) to discharge. Secondary objectives included examining their impact on measures of ED throughput for non-resuscitative patients: ED length of stay (LOS), door-to-physician time and left-without-being-seen rates (LWBS). METHODS: In this retrospective study, 6845 clinical shifts worked by 20 EPs at a community ED in Newmarket, Canada from 1 January 2012 to 31 March 2015 were evaluated. Using a clustered design, we compared productivity measures between shifts with and without Physician Navigators, by physician. We used a linear mixed model to examine mean changes in Pt/hr and TAT to discharge for EPs who employed Physician Navigators. For secondary objectives, autoregressive modelling was performed to compare ED throughput metrics before and after the implementation of Physician Navigators for non-resuscitative patients. RESULTS: Patient volumes increased by 20 patients per day (p<0.001). Mean Pt/hr increased by 1.07 patients per hour (0.98 to 1.16, p<0.001). The mean TAT to discharge decreased by 10.6 min (-13.2 to -8.0, p<0.001). After implementation of the Physician Navigator programme, overall mean LOS for non-resuscitative patients decreased by 2.6 min (p=0.007), and mean door-to-physician time decreased by 7.4 min (p<0.001). LBWS rates decreased from 1.13% to 0.63% of daily patient volume (p<0.001). CONCLUSION: Despite an ED volume increase, the use of a Physician Navigator was associated with significant improvements in EP productivity, and significant reductions in ED throughput times.

The role of collective motion in examples of coarsening and self-assembly.

The simplest prescription for building a patterned structure from its constituents is to add particles, one at a time, to an appropriate template. However, self-organizing molecular and colloidal systems in nature can evolve in much more hierarchical ways. Specifically, constituents (or clusters of constituents) may aggregate to form clusters (or clusters of clusters) that serve as building blocks for later stages of assembly. Here we evaluate the character and consequences of such collective motion in a set of prototypical assembly processes. We do so using computer simulations in which a system's capacity for hierarchical dynamics can be controlled systematically. By explicitly allowing or suppressing collective motion, we quantify its effects. We find that coarsening within a two dimensional attractive lattice gas (and an analogous off-lattice model in three dimensions) is naturally dominated by collective motion over a broad range of temperatures and densities. Under such circumstances, cluster mobility inhibits the development of uniform coexisting phases, especially when macroscopic segregation is strongly favored by thermodynamics. By contrast, the assembly of model viral capsids is not frustrated but is instead facilitated by collective moves, which promote the orderly binding of intermediates consisting of several monomers.

Far-from-equilibrium measurements of thermodynamic length.

Thermodynamic length is a path function that generalizes the notion of length to the surface of thermodynamic states. Here, we show how to measure thermodynamic length in far-from-equilibrium experiments using the work fluctuation relations. For these microscopic systems, it proves necessary to define the thermodynamic length in terms of the Fisher information. Consequently, the thermodynamic length can be directly related to the magnitude of fluctuations about equilibrium. The work fluctuation relations link the work and the free-energy change during an external perturbation on a system. We use this result to determine equilibrium averages at intermediate points of the protocol in which the system is out of equilibrium. This allows us to extend Bennett's method to determine the potential of the mean force, as well as the thermodynamic length, in single-molecule experiments.

Effect of ion distribution on conductivity of block copolymer electrolytes.

Energy-filtered transmission electron microscopy (EFTEM) was used to determine the distribution of lithium ions in solid polymer electrolytes for lithium batteries. The electrolytes of interest are mixtures of bis(trifluoromethane)sulfonimide lithium salt and symmetric poly(styrene-block-ethylene oxide) copolymers (SEO). In contrast to current solid and liquid electrolytes, the conductivity of SEO/salt mixtures increases with increasing molecular weight of the copolymers. EFTEM results show that the salt is increasingly localized in the middle of the poly(ethylene oxide) (PEO) lamellae as the molecular weight of the copolymers is increased. Calculations of the inhomogeneous local stress field in block copolymer microdomains, modeled using self-consistent field theory, provide a quantitative explanation for this observation. These stresses, which increase with increasing molecular weight, interfere with the ability of PEO chains to coordinate with lithium cations near the walls of the PEO channels where ion mobility is expected to be low.

Length of time's arrow.

An unresolved problem in physics is how the thermodynamic arrow of time arises from an underlying time reversible dynamics. We contribute to this issue by developing a measure of time-symmetry breaking, and by using the work fluctuation relations, we determine the time asymmetry of recent single molecule RNA unfolding experiments. We define time asymmetry as the Jensen-Shannon divergence between trajectory probability distributions of an experiment and its time-reversed conjugate. Among other interesting properties, the length of time's arrow bounds the average dissipation and determines the difficulty of accurately estimating free energy differences in nonequilibrium experiments.

Diagrammatic kinetic theory for a lattice model of a liquid. I. Theory.

We present a diagrammatic formalism for the time correlation functions of density fluctuations for an excluded volume lattice gas on a simple d-dimensional hypercubic lattice. We consider a multicomponent system in which particles of different species can have different transition rates. Our theoretical approach uses a Hilbert space formalism for the time dependent dynamical variables of a stochastic process that satisfies the detailed balance condition. We construct a Liouville matrix consistent with the dynamics of the model to calculate both the equation of motion for multipoint densities in configuration space and the interactions in the diagrammatic theory. A Boley basis of fluctuation vectors for the Hilbert space is used to develop two formally exact diagrammatic series for the time correlation functions. These theoretical techniques are generalizations of methods previously used for spin systems and atomic liquids, and they are generalizable to more complex lattice models of liquids such as a lattice gas with attractive interactions or polymer models. We use our formalism to construct approximate kinetic theories for the van Hove correlation and self-correlation function. The most simple approximation is the mean field approximation, which is exact for the van Hove correlation function of a one component system but an approximation for the self-correlation function. We use our first diagrammatic series to derive a two site multiple scattering approximation that gives a simple analytic expression for the spatial Fourier transform of the self-correlation function. We employ our second diagrammatic series to derive a simple mode coupling type approximation that provides a system of equations that can be solved for the self-correlation function.

Diagrammatic kinetic theory for a lattice model of a liquid. II. Comparison of theory and simulation results.

We compare the predictions of the mean field, the two site multiple scattering, and the simple mode coupling approximation developed in the previous paper for the dynamics of a tagged particle in an excluded volume lattice gas with the results of computer simulations. The tagged particle has a transition rate of gamma while the background particles have transition rates of alphagamma. We consider the tracer diffusion coefficient and the incoherent intermediate scattering function (IISF) for low, intermediate, and high concentrations of particles and for simple square and cubic lattices. In general, the approximate kinetic theories are more accurate in predicting simulations results at low concentrations, high dimensions, and large alpha. For the tracer diffusion coefficient, the mean field approximation is the least accurate, the two site multiple scattering approximation is more accurate, and the simple mode coupling approximation is the most accurate; all three approximate theories overestimate the simulation results. For the IISF, the mean field approximation is quantitatively accurate in the limit of small concentration and large alpha but in general decays too quickly. The two site multiple scattering approximation is quantitatively accurate at low and intermediate concentrations for large wave vectors; it is always more accurate than the mean field approximation and always decays more quickly than the simulation results. The simple mode coupling approximation is the most accurate of the three approximations in most cases and especially so for small wave vectors, high concentration, and small alpha; unfortunately, its predictions are not quantitatively accurate in these highly nonmean field regimes. We discuss the implications of these results for developing diagrammatic kinetic theories.