On the origin of the extremely different solubilities of polyethers in water

The solubilities of polyethers are surprisingly counter-intuitive. The best-known example is the difference between polyethylene glycol ([–CH2–CH2–O–]n) which is infinitely soluble, and polyoxymethylene ([–CH2–O–]n) which is completely insoluble in water, exactly the opposite of what one expects from the C/O ratios of these molecules. Similar anomalies exist for oligomeric and cyclic polyethers. To solve this apparent mystery, we use femtosecond vibrational and GHz dielectric spectroscopy with complementary ab initio calculations and molecular dynamics simulations. We find that the dynamics of water molecules solvating polyethers is fundamentally different depending on their C/O composition. The ab initio calculations and simulations show that this is not because of steric effects (as is commonly believed), but because the partial charge on the O atoms depends on the number of C atoms by which they are separated. Our results thus show that inductive effects can have a major impact on aqueous solubilities

Predicting RP-LC retention indices of structurally unknown chemicals from mass spectrometry data

Non-target analysis combined with liquid chromatography high resolution mass spectrometry is considered one of the most comprehensive strategies for the detection and identification of known and unknown chemicals in complex samples. However, many compounds remain unidentified due to data complexity and limited number structures in chemical databases. In this work, we have developed and validated a novel machine learning algorithm to predict the retention index (ri) values for structurally (un)known chemicals bIased on their measured fragmentation pattern. The developed model, for the first time, enabled the predication of r values without the need for the exact structure of the chemicals, with an R2 of 0.91 and 0.77 and root mean squared error (RMSE) of 47 and 67 ri  units for the NORMAN (n = 3131) and amide (n = 604) test sets, respectively. This fragment based model showed comparable accuracy in ri  prediction compared to conventional descriptor-based models that rely on known chemical structure, which obtained an R2 of 0.85 with an RMSE of 67

Temporal relationship between instantaneous pressure gradients and peak‐to‐peak systolic ejection gradient in congenital aortic stenosis

ObjectiveWe sought to identify a time during cardiac ejection when the instantaneous pressure gradient (IPG) correlated best, and near unity, with peak‐to‐peak systolic ejection gradient (PPSG) in patients with congenital aortic stenosis. Noninvasive echocardiographic measurement of IPG has limited correlation with cardiac catheterization measured PPSG across the spectrum of disease severity of congenital aortic stenosis. A major contributor is the observation that these measures are inherently different with a variable relationship dependent on the degree of stenosis.DesignHemodynamic data from cardiac catheterizations utilizing simultaneous pressure measurements from the left ventricle (LV) and ascending aorta (AAo) in patients with congenital valvar aortic stenosis was retrospectively reviewed over the past 5 years. The cardiac cycle was standardized for all patients using the percentage of total LV ejection time (ET). Instantaneous gradient at 5% intervals of ET were compared to PPSG using linear regression and Bland‐Altman analysis.ResultsA total of 22 patients underwent catheterization at a median age of 13.7 years (interquartile range [IQR] 10.3‐18.0) and median weight of 51.1 kg (IQR 34.2‐71.6). The PPSG was 46.5 ± 12.6 mm Hg (mean ± SD) and correlated suboptimally with the maximum and mean IPG. The midsystolic IPG (occurring at 50% of ET) had the strongest correlation with the PPSG (PPSG = 0.97(IPG50%)–1.12, R2 = 0.88), while the IPG at 55% of ET was closest to unity (PPSG = 0.997(IPG55%)–1.17, R2 = 0.87).ConclusionsThe commonly measured maximum and mean IPG are suboptimal estimates of the PPSG in congenital aortic stenosis. Using catheter‐based data, IPG at 50%–55% of ejection correlates well with PPSG. This may allow for a more accurate estimation of PPSG via noninvasive assessment of IPG.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140042/1/chd12514.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/140042/2/chd12514_am.pd

Nonequilibrium candidate Monte Carlo: A new tool for efficient equilibrium simulation

Metropolis Monte Carlo simulation is a powerful tool for studying the equilibrium properties of matter. In complex condensed-phase systems, however, it is difficult to design Monte Carlo moves with high acceptance probabilities that also rapidly sample uncorrelated configurations. Here, we introduce a new class of moves based on nonequilibrium dynamics: candidate configurations are generated through a finite-time process in which a system is actively driven out of equilibrium, and accepted with criteria that preserve the equilibrium distribution. The acceptance rule is similar to the Metropolis acceptance probability, but related to the nonequilibrium work rather than the instantaneous energy difference. Our method is applicable to sampling from both a single thermodynamic state or a mixture of thermodynamic states, and allows both coordinates and thermodynamic parameters to be driven in nonequilibrium proposals. While generating finite-time switching trajectories incurs an additional cost, driving some degrees of freedom while allowing others to evolve naturally can lead to large enhancements in acceptance probabilities, greatly reducing structural correlation times. Using nonequilibrium driven processes vastly expands the repertoire of useful Monte Carlo proposals in simulations of dense solvated systems

The effect of high dose antibiotic impregnated cement on rate of surgical site infection after hip hemiarthroplasty for fractured neck of femur : a protocol for a double-blind quasi randomised controlled trial

Background: Mortality following hip hemiarthroplasty is in the range of 10-40% in the first year, with much attributed to post-operative complications. One such complication is surgical site infection (SSI), which at the start of this trial affected 4.68% of patients in the UK having this operation. Compared to SSI rates of elective hip surgery, at less than 1%, this figure is elevated. The aim of this quasi randomised controlled trial (RCT) is to determine if high dose antibiotic impregnated cement can reduce the SSI in patients at 12-months after hemiarthroplasty for intracapsular fractured neck of femur. Methods: 848 patients with an intracapsular fractured neck of femur requiring a hip hemiarthroplasty are been recruited into this two-centre double-blind quasi RCT. Participants were recruited before surgery and quasi randomised to standard care or intervention group. Participants, statistician and outcome assessors were blind to treatment allocation throughout the study. The intervention consisted of high dose antibiotic impregnated cement consisting of 1 gram Clindamycin and 1 gram of Gentamicin. The primary outcome is Health Protection Agency (HPA) defined deep surgical site infection at 12 months. Secondary outcomes include HPA defined superficial surgical site infection at 30 days, 30 and 90-day mortality, length of hospital stay, critical care stay, and complications. Discussion: Large randomised controlled trials assessing the effectiveness of a surgical intervention are uncommon, particularly in the speciality of orthopaedics. The results from this trial will inform evidence-based recommendations for antibiotic impregnated cement in the management of patients with a fractured neck of femur undergoing a hip hemiarthroplasty. If high dose antibiotic impregnated cement is found to be an effective intervention, implementation into clinical practice could improve long-term outcomes for patients undergoing hip hemiarthroplasty

Local Orientational Order in Liquids Revealed by Resonant Vibrational Energy Transfer

We demonstrate that local orientational ordering in a liquid can be observed in the decay of the vibrational anisotropy caused by resonant transfer of vibrational excitations between its constituent molecules. We show that the functional form of this decay is determined by the (distribution of) angles between the vibrating bonds of the molecules between which energy transfer occurs, and that the initial drop in the decay reflects the average angle between nearest neighbors. We use this effect to observe the difference in local orientational ordering in the two hydrogen-​bonded liquids ethanol and N-​methylacetamide

Colored-noise thermostats \`a la carte

Recently, we have shown how a colored-noise Langevin equation can be used in the context of molecular dynamics as a tool to obtain dynamical trajectories whose properties are tailored to display desired sampling features. In the present paper, after having reviewed some analytical results for the stochastic differential equations forming the basis of our approach, we describe in detail the implementation of the generalized Langevin equation thermostat and the fitting procedure used to obtain optimal parameters. We discuss in detail the simulation of nuclear quantum effects, and demonstrate that, by carefully choosing parameters, one can successfully model strongly anharmonic solids such as neon. For the reader's convenience, a library of thermostat parameters and some demonstrative code can be downloaded from an on-line repository

LIM-kinase1 Hemizygosity Implicated in Impaired Visuospatial Constructive Cognition

AbstractTo identify genes important for human cognitive development, we studied Williams syndrome (WS), a developmental disorder that includes poor visuospatial constructive cognition. Here we describe two families with a partial WS phenotype; affected members have the specific WS cognitive profile and vascular disease, but lack other WS features. Submicroscopic chromosome 7q11.23 deletions cosegregate with this phenotype in both families. DNA sequence analyses of the region affected by the smallest deletion (83.6 kb) revealed two genes, elastin (ELN ) and LIM-kinase1 (LIMK1). The latter encodes a novel protein kinase with LIM domains and is strongly expressed in the brain. Because ELN mutations cause vascular disease but not cognitive abnormalities, these data implicate LIMK1 hemizygosity in impaired visuospatial constructive cognition