Essential dynamics (ED) is a useful method for analyzing trajectories generated by molecular dynamics (MD), but current tools are awkward to use, limiting the usefulness of the technique. This paper ...describes a new interactive graphical interface for visualization of ED results, including filtering a trajectory on an arbitrary set of eigenvectors and manipulation of a structure's projection along any eigenvector.
Despite low prevalence of pulmonary embolism (PE) in young adults, they are frequently imaged for PE, which involves radiation exposure and substantial financial cost.
Determine the use and positive ...proportions for PE imaging by age, differences in clinical presentation of PE by age and the projected impact of an age-targeted decision rule.
Analysis of two national population-based datasets: the 2009 Nationwide Emergency Department Sample, a 20% sample of US emergency departments (EDs) and the 2003-2006 Pulmonary Embolism Rule-out Criteria (PERC) dataset, a multisite cohort of ED patients with suspected PE from 12 US EDs.
Prevalence of PE was 10 times lower in young patients (18-35 years) than in older patients (>65 years) (0.06% vs 0.60%, p<0.001), but young patients were imaged for PE almost as frequently as older patients (2.3% vs 3.2%). This resulted in a lower proportion of positive examinations in young adults than older adults (2.3% vs 17.4%, p<0.001 in women; 4.0% vs 21.4%, p<0.001 in men). Clinical predictors of PE varied by age. Tachycardia was a significant predictor of PE in older patients (OR: 1.2-1.9, p<0.001), but not young patients. Fever was a significant predictor only in young patients (OR: 1.4-7.2, p<0.01). A modification of the previously described PERC rule to include age-specific risk factors could reduce PE imaging by 51% in young patients, with a missed PE rate of 0.6% in those excluded from imaging.
Young patients are frequently imaged for PE and have lower positive imaging rates than older patients. After further validation, application of our proposed rule for excluding young patients from PE imaging could reduce imaging, increase the positive rate of imaging and result in a low rate of missed PE among those excluded from imaging.
Generalized Born (GB) models provide a computationally efficient means of representing the electrostatic effects of solvent and are widely used, especially in molecular dynamics (MD). A class of ...particularly fast GB models is based on integration over an interior volume approximated as a pairwise union of atom sphereseffectively, the interior is defined by a van der Waals rather than Lee-Richards molecular surface. The approximation is computationally efficient but, if uncorrected, allows for high dielectric (water) regions smaller than a water molecule between atoms, leading to decreased accuracy. Here, an earlier pairwise GB model is extended by a simple analytic correction term that largely alleviates the problem by correctly describing the solvent-excluded volume of each pair of atoms. The correction term introduces a free energy barrier to the separation of nonbonded atoms. This free energy barrier is seen in explicit solvent and Lee-Richards molecular surface implicit solvent calculations but has been absent from earlier pairwise GB models. When used in MD, the correction term yields protein hydrogen bond length distributions and polypeptide conformational ensembles that are in better agreement with explicit solvent results than earlier pairwise models. The robustness and simplicity of the correction preserves the efficiency of the pairwise GB models while making them a better approximation to reality.
Previously, we found that the use of ultrasonography for patients with suspected nephrolithiasis resulted in similar outcomes and less radiation exposure vs. CT scan. In this study, we evaluated the ...implementation of an ultrasound-first clinical decision support (CDS) tool in patients with suspected nephrolithiasis.
This randomized trial was conducted at an academic emergency department (ED). We implemented the ultrasound-first CDS tool, deployed when an ED provider placed a CT order for suspected nephrolithiasis. Providers were randomized to receiving the CDS tool vs. usual care. The primary outcome was receipt of CT during the index ED visit. Secondary outcomes included radiation dose and ED revisit.
64 ED Providers and 254 patients with suspected nephrolithiasis were enrolled from January 2019 through Dec 2020. The US-First CDS tool was deployed for 128 patients and was not deployed for 126 patients. 86.7% of patients in the CDS arm received a CT vs. 94.4% in the usual care arm, resulting in an absolute risk difference of −7.7% (−14.8 to −0.6%). Mean radiation dose in the CDS arm was 6.8 mSv (95% CI 5.7–7.9 mSv) vs. 6.1 mSv (95% CI 5.1–7.1 mSv) in the usual care arm. The CDS arm did not result in increased ED revisits, CT scans, or hospitalizations at 7 or 30 days.
Implementation of the US-first CDS tool resulted in lower CT use for ED patients with suspected nephrolithiasis. The use of this decision support may improve the evaluation of a common problem in the ED.
Trial Registration:ClinicalTrials.gov#NCT03461536
•In this trial of participants with suspected nephrolithiasis, randomization to a decision support tool resulted in fewer CT scans vs. usual care.•There was no increase in emergency department revisits at three, seven, or thirty days.•Implementation of the US-first CDS tool may decrease CT scan use for ED patients with suspected nephrolithiasis.•Confirmation in a multi-center study is warranted.
Like temperature and pressure, the solution pH is an important thermodynamic variable that is commonly varied in experiments and is used by cells to influence biochemical function. It is now becoming ...feasible to carry out practical molecular dynamics simulations that mimic the thermodynamics of such experiments, by allowing proton transfer between the system of interest and a hypothetical bath of protons at a given pH. These are demanding calculations, because the energetics of charge changes upon protonation or deprotonation must be accurately modeled, and because such simulations must sample both molecular configurations and the large number of protonation states that are possible for a molecule with many titrating sites.
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