4†Peripapillary hyperreflective ovoid mass-like structures (PHOMS) in children: optical coherence tomography measurements and refractive status.

Peripapillary hyperreflective ovoid mass-like structures (PHOMS) are a recently described entity. They are a common and non-specific cause of pseudopapilloedema. We aim to determine if there is a relationship between optical coherence tomography (OCT) measurements and refractive status on the presence of PHOMS.Retrospective analysis of optic nerve head OCT scans from children seen in the suspected papilledema virtual clinic between August 2016 and March 2021 at University Hospital of Wales, Cardiff. Three assessors graded each scan for the presence of PHOMS. Numerical data on the disc morphology (disc area (DA (mm2)) and scleral canal diameter (SCD (µm)) was obtained from the OCT scans. Refractive data was obtained from the initial optometric referral where available. Logistic regression analysis was performed to assess the effect of age, sex, spherical equivalent, DA and SCD on the likelihood of the presence of PHOMS.The SCD was significantly larger in eyes with PHOMS (mean diameter 1771 µm) vs no PHOMS (mean diameter 1621 µm). Odds ratio 1.0042 (1.0016 to 1.0069). The other variables were not significantly associated, but there was a tendency towards a younger age, larger disc area and the presence of a refractive error if PHOMS were present.Anatomical and developmental differences in the size of the scleral canal and optic nerve may explain the presence of PHOMS in children. In contrast to other recently published studies, we show that a wider scleral canal diameter was significantly associated with the presence of PHOMS.

Shapes of Nonsymmetric Capillary Bridges.

Here we study the shapes of droplets captured between chemically distinct parallel plates. This work is a preliminary step toward characterizing the influence of second-phase bridging between biomolecular surfaces on their solution contacts, i.e., capillary attraction or repulsion. We obtain a simple, variable-separated quadrature formula for the bridge shape. The technical complication of double-ended boundary conditions on the shapes of nonsymmetric bridges is addressed by studying waists in the bridge shape, i.e., points where the bridge silhouette has zero derivative. Waists are generally expected with symmetric bridges, but waist points can serve to characterize shape segments in general cases. We study how waist possibilities depend on the physical input to these problems, noting that these formulas change with the sign of the inside-outside pressure difference of the bridge. These results permit a variety of different interesting shapes, and the development below is accompanied by several examples.

Hydration Mimicry by Membrane Ion Channels.

Ions transiting biomembranes might pass readily from water through ion-specific membrane proteins if these protein channels provide environments similar to the aqueous solution hydration environment. Indeed, bulk aqueous solution is an important reference condition for the ion permeation process. Assessment of this hydration mimicry concept depends on understanding the hydration structure and free energies of metal ions in water in order to provide a comparison for the membrane channel environment. To refine these considerations, we review local hydration structures of ions in bulk water and the molecular quasi-chemical theory that provides hydration free energies. In doing so, we note some current views of ion binding to membrane channels and suggest new physical chemical calculations and experiments that might further clarify the hydration mimicry concept.

Quasi-Chemical Theory with Cluster Sampling from Ab Initio Molecular Dynamics: Fluoride (F-) Anion Hydration.

Accurate predictions of the hydration free energy for anions typically has been more challenging than that for cations. Hydrogen bond donation to the anion in hydrated clusters such as F(H2O) n - can lead to delicate structures. Consequently, the energy landscape contains many local minima, even for small clusters, and these minima present a challenge for computational optimization. Utilization of cluster experimental results for the free energies of gas-phase clusters shows that even though anharmonic effects are interesting they need not be of troublesome magnitudes for careful applications of quasi-chemical theory to ion hydration. Energy-optimized cluster structures for anions can leave the central ion highly exposed, and application of implicit solvation models to these structures can incur more serious errors than those for metal cations. Utilizing cluster structures sampled from ab initio molecular dynamics simulations substantially fixes those issues.

Comparison of single-ion molecular dynamics in common solvents.

Laying a basis for molecularly specific theory for the mobilities of ions in solutions of practical interest, we report a broad survey of velocity autocorrelation functions (VACFs) of Li+ and PF6- ions in water, ethylene carbonate, propylene carbonate, and acetonitrile solutions. We extract the memory function, γ(t), which characterizes the random forces governing the mobilities of ions. We provide comparisons controlling for the effects of electrolyte concentration and ion-pairing, van der Waals attractive interactions, and solvent molecular characteristics. For the heavier ion (PF6-), velocity relaxations are all similar: negative tail relaxations for the VACF and a clear second relaxation for γt, observed previously also for other molecular ions and with n-pentanol as the solvent. For the light Li+ ion, short time-scale oscillatory behavior masks simple, longer time-scale relaxation of γt. But the corresponding analysis of the solventberg Li+H2O4 does conform to the standard picture set by all the PF6- results.

Molecular-Scale Description of SPAN80 Desorption from a Squalane-Water Interface.

Extensive all-atom molecular dynamics calculations on the water-squalane interface for nine different loadings with sorbitan monooleate (SPAN80), at T = 300 K, are analyzed for the surface tension equation of state, desorption free-energy profiles as they depend on loading, and to evaluate escape times for adsorbed SPAN80 into the bulk phases. These results suggest that loading only weakly affects accommodation of a SPAN80 molecule by this squalane-water interface. Specifically, the surface tension equation of state is simple through the range of high tension to high loading studied, and the desorption free-energy profiles are weakly dependent on loading here. The perpendicular motion of the centroid of the SPAN80 headgroup ring is well-described by a diffusional model near the minimum of the desorption free-energy profile. Lateral diffusional motion is weakly dependent on loading. Escape times evaluated on the basis of a diffusional model and the desorption free energies are 7 × 10-2 s (into the squalane) and 3 × 102 h (into the water). The latter value is consistent with desorption times of related lab-scale experimental work.

A facility for the analysis of the electronic structures of solids and their surfaces by synchrotron radiation photoelectron spectroscopy.

A synchrotron radiation beamline in the photon energy range of 18-240 eV and an electron spectroscopy end station have been constructed at the 3 GeV Diamond Light Source storage ring. The instrument features a variable polarisation undulator, a high resolution monochromator, a re-focussing system to form a beam spot of 50 × 50 µm2, and an end station for angle-resolved photoelectron spectroscopy (ARPES) including a 6-degrees-of-freedom cryogenic sample manipulator. The beamline design and its performance allow for a highly productive and precise use of the ARPES technique at an energy resolution of 10-15 meV for fast k-space mapping studies with a photon flux up to 2 ⋅ 1013 ph/s and well below 3 meV for high resolution spectra.

Integrated carbon, sulfur, and nitrogen isotope chemostratigraphy of the Ediacaran Lantian Formation in South China: Spatial gradient, ocean redox oscillation, and fossil distribution.

The Ediacaran Doushantuo Formation in South China is a prime target for geobiological investigation because it offers opportunities to integrate chemostratigraphic and paleobiological data. Previous studies were mostly focused on successions in shallow-water shelf facies, but data from deep-water successions are needed to fully understand basinal redox structures. Here, we report δ13 Ccarb , δ13 Corg , δ34 Spyr , δ34 SCAS , and δ15 Nsed data from a drill core of the fossiliferous Lantian Formation, which is a deep-water equivalent of the Doushantuo Formation. Our data confirm a large (>10‰) spatial gradient in δ13 Ccarb in the lower Doushantuo/Lantian formations, but this gradient is probably due to the greater sensitivity of carbonate-poor deep-water sediments to isotopic mixing with 13 C-depleted carbonate cements. A pronounced negative δ13 Ccarb excursion (EN3) in the upper Doushantuo/Lantian formations, however, is spatially consistent and may be an equivalent of the Shuram excursion. δ34 Spyr is more negative in deeper-water facies than in shallow-water facies, particularly in the lower Doushantuo/Lantian formations, and this spatial pattern is interpreted as evidence for ocean redox stratification: Pyrite precipitated in euxinic deep waters has lower δ34 Spyr than that formed within shallow-water sediments. The Lantian Formation was probably deposited in oscillating oxic and euxinic conditions. Euxinic black shales have higher TOC and TN contents, but lower δ34 Spyr and δ15 Nsed values. In euxinic environments, pyrite was predominantly formed in the water column and organic nitrogen was predominantly derived from nitrogen fixation or NH4+ assimilation because of quantitative denitrification, resulting in lower δ34 Spyr and δ15 Nsed values. Benthic macroalgae and putative animals occur exclusively in euxinic black shales. If preserved in situ, these organisms must have lived in brief oxic episodes punctuating largely euxinic intervals, only to be decimated and preserved when the local environment switched back to euxinia again. Thus, taphonomy and ecology were the primary factors controlling the stratigraphic distribution of macrofossils in the Lantian Formation.

Hydrogen Isotopic Composition of Arctic and Atmospheric CH4 Determined by a Portable Near-Infrared Cavity Ring-Down Spectrometer with a Cryogenic Pre-Concentrator.

In this study, near-infrared continuous wave cavity ring-down spectroscopy was applied to the measurement of the δ2H of methane (CH4). The cavity ring-down spectrometer (CRDS) system consisted of multiple DFB laser diodes to optimize selection of spectral line pairs. By rapidly switching measurements between spectral line peaks and the baseline regions, the long-term instrumental drift was minimized, substantially increasing measurement precision. The CRDS system coupled with a cryogenic pre-concentrator measured the δ2H of terrestrial atmospheric CH4 from 3 standard liters of air with a precision of ±1.7‰. The rapidity with which both C and H isotopic measurements of CH4 can be made with the CRDS will enable hourly monitoring of diurnal variations in terrestrial atmospheric CH4 signatures that can be used to increase the resolution of global climate models for the CH4 cycle. Although the current instrument is not capable of measuring the δ2H of 10 ppbv of martian CH4, current technology does exist that could make this feasible for future spaceflight missions. As biological and abiotic CH4 sources have overlapping carbon isotope signatures, dual-element (C and H) analysis is key to reliable differentiation of these sources. Such an instrument package would therefore offer improved ability to determine whether or not the CH4 recently detected in the martian atmosphere is biogenic in origin. Key Words: Arctic-Hydrogen isotopes-Atmospheric CH4-CRDS-Laser. Astrobiology 16, 787-797.

Assent for children's participation in research: why it matters and making it meaningful.

BACKGROUND: There are gaps in the existing evidence base about assent, with conflicting and unhelpful views prevalent. We contend that appropriate assent is a valuable process that has important consequences for children's/young people's participation in research. Furthermore, there is a need for a model to support researchers in making decisions about who to assent and how to do this is a meaningful way. METHODS: We undertook a scoping review of the literature to assess the body of opinion on assent in research with children/young people. An anonymous online survey was conducted to gather views from the wider community undertaking research with children/young people. We also sought to gather examples of current and effective practice that could be shared beyond the level of a single institution and our own experience. Survey participants included 48 health professionals with varied levels of experience, all actively involved in research with children. RESULTS: Published work, the findings from the online survey and our knowledge as experienced researchers in the field have confirmed four domains that should be considered in order for assent to be meaningful and individualized: child-related factors, family dynamics, study design and complexity and researcher and organizational factors. Mapping these domains onto the three paradigm cases for decision-making around children and young people's assent/consent as recommended by the Nuffield Council on Bioethics has resulted in a model that will aid researchers in understanding the relationship between assent and consent and help them make decisions about when assent is appropriate. CONCLUSIONS: The debate about assent needs to move away from terminology, definition and legal issues. It should focus instead on practical ways of supporting researchers to work in partnership with children, thus ensuring a more informed, voluntary and more robust and longer lasting commitment to research.

Molecular Theory and the Effects of Solute Attractive Forces on Hydrophobic Interactions.

The role of solute attractive forces on hydrophobic interactions is studied by coordinated development of theory and simulation results for Ar atoms in water. We present a concise derivation of the local molecular field (LMF) theory for the effects of solute attractive forces on hydrophobic interactions, a derivation that clarifies the close relation of LMF theory to the EXP approximation applied to this problem long ago. The simulation results show that change from purely repulsive atomic solute interactions to include realistic attractive interactions diminishes the strength of hydrophobic bonds. For the Ar-Ar rdfs considered pointwise, the numerical results for the effects of solute attractive forces on hydrophobic interactions are opposite in sign and larger in magnitude than predicted by LMF theory. That comparison is discussed from the point of view of quasichemical theory, and it is suggested that the first reason for this difference is the incomplete evaluation within LMF theory of the hydration energy of the Ar pair. With a recent suggestion for the system-size extrapolation of the required correlation function integrals, the Ar-Ar rdfs permit evaluation of osmotic second virial coefficients B2. Those B2's also show that incorporation of attractive interactions leads to more positive (repulsive) values. With attractive interactions in play, B2 can change from positive to negative values with increasing temperatures. This is consistent with the puzzling suggestions of decades ago that B2 ≈ 0 for intermediate cases of temperature or solute size. In all cases here, B2 becomes more attractive with increasing temperature.

Resonance phenomena in a time-dependent, three-dimensional model of an idealized eddy.

We analyze the geometry of Lagrangian motion and material barriers in a time-dependent, three-dimensional, Ekman-driven, rotating cylinder flow, which serves as an idealization for an isolated oceanic eddy and other overturning cells with cylindrical geometry in the ocean and atmosphere. The flow is forced at the top through an oscillating upper lid, and the response depends on the frequency and amplitude of lid oscillations. In particular, the Lagrangian geometry changes near the resonant tori of the unforced flow, whose frequencies are rationally related to the forcing frequencies. Multi-scale analytical expansions are used to simplify the flow in the vicinity of resonant trajectories and to investigate the resonant flow geometries. The resonance condition and scaling can be motivated by simple physical argument. The theoretically predicted flow geometries near resonant trajectories have then been confirmed through numerical simulations in a phenomenological model and in a full solution of the Navier-Stokes equations.

Tumor burden evaluation in NF1 patients with plexiform neurofibromas in daily clinical practice.

BACKGROUND: Existing volumetric measurements of plexiform neurofibromas (PNs) are time consuming and error prone, as they require delineation of PN boundaries, a procedure that is not practical in the typical clinical setting. The aim of this study is to assess the Plexiform Neurofibroma Instant Segmentation Tool (PNist), a novel semi-automated segmentation program that we developed for PN delineation in a clinical context. PNist was designed to greatly simplify volumetric assessment of PNs through use of an intuitive user interface while providing objectively consistent results with minimal interobserver and intraobserver variabilities in reasonable time. MATERIALS AND METHODS: PNs were measured in 30 magnetic resonance imaging (MRI) scans from 12 patients with neurofibromatosis 1. Volumetric measurements were performed using PNist and compared to a standard semi-automated volumetric method (Analyze 9.0). RESULTS: High correlation was detected between PNist and the semi-automated method (R(2) = 0.996), with a mean volume overlap error of 9.54 % and low intraobserver and interobserver variabilities. The segmentation time required for PNist was 60 % of the time required for Analyze 9.0 (360 versus 900 s, respectively). PNist was also reliable when assessing changes in tumor size over time, compared to the existing commercial method. CONCLUSIONS: Our study suggests that the new PNist method is accurate, intuitive, and less time consuming for PN segmentation compared to existing commercial volumetric methods. The workflow is simple and user-friendly, making it an important clinical tool to be used by radiologists, neurologists and neurosurgeons on a daily basis, helping them deal with the complex task of evaluating PN burden and progression.

Loop-Closure and Gaussian Models of Collective Structural Characteristics of Capped PEO Oligomers in Water.

Parallel-tempering MD results for a CH3(CH2-O-CH2)mCH3 chain in water are exploited as a database for analysis of collective structural characteristics of the PEO globule with a goal of defining models permitting statistical thermodynamic analysis of dispersants of Corexit type. The chain structure factor, relevant to neutron scattering from a deuterated chain in null water, is considered specifically. The traditional continuum-Gaussian structure factor is inconsistent with the simple k → ∞ behavior, but we consider a discrete-Gaussian model that does achieve that consistency. Shifting and scaling the discrete-Gaussian model helps to identify the low-k to high-k transition near k ≈ 2π/0.6 nm when an empirically matched number of Gaussian links is about one-third of the total number of effective atom sites. This short distance-scale boundary of 0.6 nm is directly verified with the r space distributions, and this distance is thus identified with a natural size for coarsened monomers. The probability distribution of Rg(2) is compared with the classic predictions for both the Gaussian model and freely jointed chains. ⟨Rg(2)(j)⟩, the contribution of the jth chain segment to ⟨Rg(2)⟩, depends on the contour index about as expected for Gaussian chains despite significant quantitative discrepancies that express the swelling of these chains in water. Monomers central to the chain contour occupy the center of the chain globule. The density profiles of chain segments relative to their center of mass can show distinctive density structuring for smaller chains due to the close proximity of central elements to the globule center. However, that density structuring washes out for longer chains where many chain elements additively contribute to the density profiles. Gaussian chain models thus become more satisfactory for the density profiles for longer chains.

Multiscale theory in the molecular simulation of electrolyte solutions.

To define a role for AIMD simulation on the limited time and space scales accessible to those demanding methods, this paper organizes McMillan-Mayer theory, the potential distribution approach, and quasi-chemical theory to provide theory for the thermodynamic effects associated with long-length scales. The theory treats composition fluctuations that would be accessed by larger-scale calculations, and also longer-ranged interactions that are of special interest for electrolyte solutions. The quasi-chemical organization breaks-up governing free energies into physically distinct contributions: packing, outer-shell, and chemical contributions. Here we study specifically the outer-shell contributions that express electrolyte screening. For that purpose we adopt a primitive model suggested by observation of ion-pairing in tetraethylammonium tetrafluoroborate dissolved in propylene carbonate. Gaussian statistical models are shown to be effective physical models for outer-shell contributions, and they are conclusive for the free energies within the quasi-chemical formulation. With the present data set the Gaussian physical approximation obtains more accurate mean activity coefficients than does the Bennett direct evaluation of that free energy.

Concentration dependence of the Flory-Huggins interaction parameter in aqueous solutions of capped PEO chains.

The dependence on volume fraction φ of the Flory-Huggins interaction parameter χwp(φ) describing the free energy of mixing of polymers in water is obtained by exploiting the connection of χwp(φ) to the chemical potential of the water, for which quasi-chemical theory is satisfactory. We test this theoretical approach with simulation data for aqueous solutions of capped PEO (polyethylene oxide) oligomers. For CH3(CH2-O-CH2)mCH3 (m = 11), χwp(φ) depends strongly on φ, consistent with experiment. These results identify coexisting water-rich and water-poor solutions at T = 300 K and p = 1 atm. Direct observation of the coexistence of these two solutions on simulation time scales supports that prediction for the system studied. This approach directly provides the osmotic pressures. The osmotic second virial coefficient for these chains is positive, reflecting repulsive interactions between the chains in the water, a good solvent for these chains.

IL15 levels on day 7 after hematopoietic cell transplantation predict chronic GVHD.

Chronic GVHD (cGVHD) is an important complication of allogeneic hematopoietic cell transplantation (HCT). As preemptive therapy might be efficacious if administered early post transplant, we set out to determine whether cGVHD can be predicted from the serum level of a biomarker on day 7 or 28. In a discovery cohort of 153 HCT recipients conditioned with BU, fludarabine and rabbit antithymocyte globulin (ATG), we determined serum levels of B-cell-activating factor, vascular endothelial growth factor, soluble TNF-α receptor 1, soluble IL2 receptor α, IL5, IL6, IL7, IL15, γ-glutamyl transpeptidase, cholinesterase, total protein, urea and ATG. Patients with low levels of IL15 (<30.6 ng/L) on day 7 had 2.7-fold higher likelihood of developing significant cGVHD (needing systemic immunosuppressive therapy) than patients with higher IL15 levels (P<0.001). This was validated in a validation cohort of 105 similarly-treated patients; those with low IL15 levels had 3.7-fold higher likelihood of developing significant cGVHD (P=0.001). Low IL15 was not associated with relapse; it trended to be associated with acute GVHD and was associated with low infection rates. In conclusion, low IL15 levels on day 7 are predictive of cGVHD, and thus could be useful in guiding preemptive therapy.

Pairing of 1-hexyl-3-methylimidazolium and tetrafluoroborate ions in n-pentanol.

Molecular dynamics simulations are obtained and analyzed to study pairing of 1-hexyl-3-methylimidazolium and tetrafluoroborate ions in n-pentanol, in particular by evaluating the potential-of-mean-force between counter ions. The present molecular model and simulation accurately predicts the dissociation constant K(d) in comparison to experiment, and thus the behavior and magnitudes for the ion-pair potential-of-mean-force at molecular distances, even though the dielectric constant of the simulated solvent differs from the experimental value by about 30%. A naive dielectric model does not capture molecule structural effects such as multiple conformations and binding geometries of the Hmim(+) and BF(4)(-) ion-pairs. Mobilities identify multiple time-scale effects in the autocorrelation of the random forces on the ions, and specifically a slow, exponential time-decay of those long-ranged forces associated here with dielectric friction effects.