The findings of a service evaluation on the practice of assessment and treatment of iron deficiency in people admitted to a UK hospital with decompensated Heart Failure.

BACKGROUND: Iron Deficiency (ID) is common in Heart Failure (HF) and associated with poor outcomes. Replacement with intravenous (IV) iron can improve functional status, quality of life and risk of unplanned admission. In 2015/16 a local service evaluation was performed which found that of people admitted with HF, only 27.5 % had assessment of iron status, and when identified, replacement occurred in fewer than half. Education strategies were employed to increase awareness of the importance of assessment and correction. OBJECTIVES: To assess if practice had improved following education strategies. METHODS: A review of 220 patient records for people admitted with HF in 2020/21 to establish if iron status assessed, presence of ID, and whether if ID identified it was treated, and by which route. Trends in 2020/21 data were explored in sub-groups by age, sex, type of HF, anaemia status, input from HF specialists and type of ID. RESULTS: Compared to 2015/16, more assessments of iron status were performed (45% vs 27.5 %), ID was corrected more frequently (57% vs 46 %) and increased use of the IV route for replacement (83% vs 58 %) CONCLUSIONS: Despite the impact of COVID-19 on usual care in 2020/21, improvement was seen in proportion of assessment and treatment of ID following simple education strategies for key stakeholders. There may be scope to improve practice further if the findings remain similar post pandemic. If so, a formal Quality Improvement approach may be helpful.

CryoEM reveals the complex self-assembly of a chemically driven disulfide hydrogel.

Inspired by the adaptability of biological materials, a variety of synthetic, chemically driven self-assembly processes have been developed that result in the transient formation of supramolecular structures. These structures form through two simultaneous reactions, forward and backward, which generate and consume a molecule that undergoes self-assembly. The dynamics of these assembly processes have been shown to differ from conventional thermodynamically stable molecular assemblies. However, the evolution of nanoscale morphologies in chemically driven self-assembly and how they compare to conventional assemblies has not been resolved. Here, we use a chemically driven redox system to separately carry out the forward and backward reactions. We analyze the forward and backward reactions both sequentially and synchronously with time-resolved cryogenic transmission electron microscopy (cryoEM). Quantitative image analysis shows that the synchronous process is more complex and heterogeneous than the sequential process. Our key finding is that a thermodynamically unstable stacked nanorod phase, briefly observed in the backward reaction, is sustained for ∼6 hours in the synchronous process. Kinetic Monte Carlo modeling show that the synchronous process is driven by multiple cycles of assembly and disassembly. The collective data suggest that chemically driven self-assembly can create sustained morphologies not seen in thermodynamically stable assemblies by kinetically stabilizing transient intermediates. This finding provides plausible design principles to develop and optimize supramolecular materials with novel properties.

Stochastic paths controlling speed and dissipation.

Natural processes occur in a finite amount of time and dissipate energy, entropy, and matter. Near equilibrium, thermodynamic intuition suggests that fast irreversible processes will dissipate more energy and entropy than slow quasistatic processes connecting the same initial and final states. For small systems, recently discovered thermodynamic speed limits suggest that faster processes will dissipate more than slower processes. Here, we test the hypothesis that this relationship between speed and dissipation holds for stochastic paths far from equilibrium. To analyze stochastic paths on finite timescales, we derive an exact expression for the path probabilities of continuous-time Markov chains from the path summation solution to the master equation. We present a minimal model for a driven system in which relative energies of the initial and target states control the speed, and the nonequilibrium currents of a cycle control the dissipation. Although the hypothesis holds near equilibrium, we find that faster processes can dissipate less under far-from-equilibrium conditions because of strong currents. This model serves as a minimal prototype for designing kinetics to sculpt the nonequilibrium path space so that faster paths produce less dissipation.

Optimizing dynamical functions for speed with stochastic paths.

Living systems are built from microscopic components that function dynamically; they generate work with molecular motors, assemble and disassemble structures such as microtubules, keep time with circadian clocks, and catalyze the replication of DNA. How do we implement these functions in synthetic nanostructured materials to execute them before the onset of dissipative losses? Answering this question requires a quantitative understanding of when we can improve performance and speed while minimizing the dissipative losses associated with operating in a fluctuating environment. Here, we show that there are four modalities for optimizing dynamical functions that can guide the design of nanoscale systems. We analyze Markov models that span the design space: a clock, ratchet, replicator, and self-assembling system. Using stochastic thermodynamics and an exact expression for path probabilities, we classify these models of dynamical functions based on the correlation of speed with dissipation and with the chosen performance metric. We also analyze random networks to identify the model features that affect their classification and the optimization of their functionality. Overall, our results show that the possible nonequilibrium paths can determine our ability to optimize the performance of dynamical functions, despite ever-present dissipation, when there is a need for speed.

Typical Stochastic Paths in the Transient Assembly of Fibrous Materials.

When chemically fueled, molecular self-assembly can sustain dynamic aggregates of polymeric fibers-hydrogels-with tunable properties. If the fuel supply is finite, the hydrogel is transient, as competing reactions switch molecular subunits between active and inactive states, drive fiber growth and collapse, and dissipate energy. Because the process is away from equilibrium, the structure and mechanical properties can reflect the history of preparation. As a result, the formation of these active materials is not readily susceptible to a statistical treatment in which the configuration and properties of the molecular building blocks specify the resulting material structure. Here, we illustrate a stochastic-thermodynamic and information-theoretic framework for this purpose and apply it to these self-annihilating materials. Among the possible paths, the framework variationally identifies those that are typical-loosely, the minimum number with the majority of the probability. We derive these paths from computer simulations of experimentally-informed stochastic chemical kinetics and a physical kinetics model for the growth of an active hydrogel. The model reproduces features observed by confocal microscopy, including the fiber length, lifetime, and abundance as well as the observation of fast fiber growth and stochastic fiber collapse. The typical mesoscopic paths we extract are less than 0.23% of those possible, but they accurately reproduce material properties such as mean fiber length.

Reading and phonological awareness in reading-disabled adults.

Sixty-eight students with reading disabilities (RDs) and 55 non-reading-disabled university undergraduates composed the sample. Students with RDs met either low achievement (LA) or regression-based discrepancy (D) criteria. In addition to IQ and reading decoding measures, all participants received measures of phonological awareness (PA), confrontation naming, and verbal fluency. Consistent with expectations, the D and LA subgroups did not differ from one another, and both performed worse than students without RD on phonological measures. However, only the LA subgroup performed worse on measures of confrontation naming and verbal fluency. Subgroups of readers who had LA without an IQ-achievement discrepancy (LA-no D) and readers who had both LA and a discrepancy (LA + D), performed worse than readers who had a discrepancy but whose reading achievement was above the 16th percentile (D-no LA) on measures of PA, naming, and fluency; this subgroup did not differ from students without RDs. These results question the utility of determining RD in adults solely on the basis of IQ-achievement discrepancy criterion without regard to other linguistic skills or absolute reading level.