Novel Z Scores to Correct Biases Due to Ventricular Volume Indexing to Body Surface Area in Adolescents and Young Adults

BackgroundReference values for cardiac magnetic resonance imaging (cMRI) in children and young adults are scarce. This leads to risk stratification of patients with congenital heart diseases being based on volumes indexed to body surface area (BSA). We aimed to produce cMRI Z score equations for ventricular volumes in children and young adults and to test whether indexing to BSA resulted in an incorrect assessment of ventricular dilation according to sex, body composition, and growth.MethodsWe retrospectively included 372 subjects aged < 26 years with either normal hearts or conditions with no impact on ventricular volumes (reference group), and 205 subjects with repaired tetralogy of Fallot (TOF) aged < 26 years. We generated Z score equations by means of multivariable regression modelling. Right ventricular dilation was assessed with the use of Z scores and compared with indexing to BSA in TOF subjects.ResultsVentricular volume Z scores were independent from age, sex, and anthropometric measurements, although volumes indexed to BSA showed significant residual association with sex and body size. In TOF subjects, indexing overestimated dilation in growing children and underestimated dilation in female compared with male subjects, and in overweight compared with lean subjects.ConclusionsIndexed ventricular volumes measured with cMRI did not completely adjust for body size and resulted in a differential error in the assessment of ventricular dilation according to sex and body size. Our proposed Z score equations solved this problem. Future studies should evaluate if ventricular volumes expressed as Z scores have a better prognostic value than volumes indexed to BSA.     

Predicting children's separation anxiety at age 6: The contributions of infant–mother attachment security,maternal sensitivity,and maternal separation anxiety

Abstract

The purpose of the present investigation was to examine the precursors and familial conditions which sustain school-aged children's separation anxiety. In a prospective, longitudinal study of 99 mother–child dyads, infancy measures of infant–mother attachment security, maternal separation anxiety, and maternal sensitivity were used to predict children's self-reported symptoms of separation anxiety at age 6. Insecurely attached children reported more separation anxiety than securely attached children. Insecure-ambivalent children reported marginally more separation anxiety than securely attached children, but not more than insecure-avoidant attached children. Regression analysis showed infant–mother attachment security and mother's sensitivity added uniquely to the prediction of children's separation anxiety, but mother's separation anxiety did not. Mediation tests show that the effect of mother's separation anxiety on children's separation anxiety may be mediated by maternal sensitivity. Research and clinical implications are discussed.     

Foam film stratification studies probe intermicellar interactions

Ultrathin foam films containing supramolecular structures like micelles in bulk and adsorbed surfactant at the liquid–air interface undergo drainage via stratification. At a fixed surfactant concentration, the stepwise decrease in the average film thickness of a stratifying micellar film yields a characteristic step size that also describes the quantized thickness difference between coexisting thick–thin flat regions. Even though many published studies claim that step size equals intermicellar distance obtained using scattering from bulk solutions, we found no reports of a direct comparison between the two length scales. It is well established that step size is inversely proportional to the cubic root of surfactant concentration but cannot be estimated by adding micelle size to Debye length, as the latter is inversely proportional to the square root of surfactant concentration. In this contribution, we contrast the step size obtained from analysis of nanoscopic thickness variations and transitions in stratifying foam films using Interferometry Digital Imaging Optical Microscopy (IDIOM) protocols, that we developed, with the intermicellar distance obtained using small-angle X-ray scattering. We find that stratification driven by the confinement-induced layering of micelles within the liquid–air interfaces of a foam film provides a sensitive probe of non-DLVO (Derjaguin–Landau–Verwey–Overbeek) supramolecular oscillatory structural forces and micellar interactions.

Molecules in simple liquids and supramolecular structures in complex fluids can stratify or undergo confinement-induced layering induced by symmetry breaking at a solid–liquid or a fluid–fluid interface (1–8). In freestanding or foam films, the confinement-induced layering of supramolecular structures including micelles (9–17), lipid layers (18, 19), polyelectrolyte–surfactant complexes (20, 21), nanoparticles (9, 22), and liquid crystalline assemblies (23) can result in drainage via stratification. Due to thin film interference, foam films visualized under white light illumination display iridescent colors for thick films (h > 100 nm) (24–28), but ultrathin films (h < 100 nm) exhibit shades of gray that get progressively darker as the film gets thinner (9–21). In reflected light microscopy, micellar foam films exhibit coexisting thick−thin regions with distinct shades of gray. Interferometry-based measurement of the average film thickness over time decreases in a stepwise fashion yielding a step size, Δh (9–17). Many published studies argue (9–12, 22, 29–34) that foam films containing charged micelles or latex particles stratify analogously due to the formation of “ordered colloidal crystals” (OCCs) and step size, Δh, equals the intermicellar distance, d, in bulk solutions. However, a comparison of concentration-dependent Δh obtained from the dynamic foam stratification studies (influenced by confinement effects) with d measured using small-angle X-ray or neutron scattering (SAXS or SANS) or other direct measurements of static equilibrium structure, and related evidence for or against the formation of OCCs in micellar foam films, are lacking in the literature. Thus, the motivations of this contribution are threefold: 1) contrast the step size, Δh, obtained via stratification studies with the intermicellar distance, d, and micelle dimensions determined using SAXS; 2) examine the SAXS data for any evidence of OCCs; and 3) elucidate the influence of ionic micelles on foam film stability and topography, as well as on colloidal forces, in multicomponent complex fluids.Micelles, formed by self-assembly of soaps and detergents and ever present in typical household foams, facilitate cleaning and detergent action by solubilizing oils and oil-soluble dirt within their hydrophobic core (2, 34, 35). Micelles formed by biosurfactants like bile salt and rhamnolipids can be used for delivering nonpolar, bio-active polyunsaturated oils, flavonoids, vitamins, and hydrophobic drugs (36–38). Therefore, understanding the stability and lifetime of micellar foams is essential toward molecular engineering of formulations, controlling foams in industrial reactors, rivers, and lakes and developing bio-surfactants (36–38). Foam film drainage involves interfacial flows that are influenced both by bulk rheology and interfacial rheology as well as Laplace or capillary pressure, Pc=σC (set by surface tension, σ and curvature, C) (27, 28, 39–41). Additionally, thickness transitions and variations in ultrathin (h < 100 nm) freestanding as well as supported (containing one or two solid boundaries) films (41–43) depend on disjoining pressure, Π(h)=−(∂G/∂h)P,T,A,Ni, defined as the free energy required to change unit thickness at constant temperature, T, pressure, P, surface area, A, and mole number, N_i (1, 34, 40–42). Intermolecular and surface forces determine the strength and range of disjoining pressure, Π(h), as well as of colloidal interaction forces, F(h) (1–3, 35, 40–42). Physical properties of surfactant solutions like surface tension and conductivity show distinct change around a critical micelle concentration (CMC), beyond which spheroidal micelles can form (2, 34, 35), and rod-like micelles, lamellar phases, etc., emerge at higher concentrations (44–46). In foam films formed with ionic surfactant at c < CMC, drainage below h < 30 nm often leads to the formation of relatively long-lived common black (CB) film attributed to counterbalancing of P_c by ΠDLVO(h), the disjoining pressure due to DLVO (Derjaguin–Landau–Verwey–Overbeek) forces contributed by van der Waals and electrostatic double-layer interactions (1–3, 35, 39, 40). Even thinner Newton black (NB) films attest to the role of shorter-range, non-DLVO surface forces (14, 25–27, 40, 41). In contrast, in micellar foam films (c > CMC), a non-DLVO, oscillatory structural force, ΠOS(h), counterbalances P_c at multiple flat thicknesses, manifested as distinct shades of gray in reflected light microscopy (9–17, 21, 40, 47–50).For micellar fluids containing charged micelles, the step size, Δh, obtained using thickness–time plots from stratification experiments, and periodicity, λ, of ΠOS(h) directly measured using thin-film balance (47, 48) show that both periodicity and step size exceed micelle size, a, implying λ>a and Δh>a. In 1971, Bruil and Lyklema (51) were the first to report that the concentration-dependent decrease in step size measured for sodium dodecyl sulfate (SDS) solutions followed a power law of the form Δh∝csoap−1/3 and wrote that step size values “seem to be related to intermolecular distance in the (unmicellized) bulk solution.” In 1988, Nikolov et al. (9) reported that foam films containing latex particles stratified in a fashion similar to micellar foam films and argued that diffusion-driven, layer-by-layer removal of micelles or particles from an ordered colloidal crystal (OCC) structure drives stratification. In their OCC or “micelle-vacancy diffusion” mechanism, they proposed that the effective film viscosity increases with decrease in stratified film thickness (9, 10, 29–31, 33). Contrastingly, in the “hydrodynamic” mechanism, Bergeron and Radke (13, 47) described stratification using a thin-film equation, by incorporating ΠOS(h) and bulk solution viscosity. Nikolov et al. (9, 10, 29–31) suggested that the step size, Δh, was equal to an effective diameter, deff=2lSDS+κ−1, computed by adding the fixed length of SDS molecules, l_SDS, to the Debye length, κ−1, that captures the range of screened electrostatic interactions. However, the step size Δh∼c−1/3 and the Debye length κ−1∼c−1/2 display distinct power laws, and the measured step size exceeds the micelle size, a, as well as the computed effective diameter, d_eff, for ionic micellar systems, or typically Δh>a and Δh>deff.Studies on charged nanoparticle dispersions find that the periodicity, λ, of the oscillatory structural force, F(h), measured directly with surface force apparatus (SFA), or colloidal probe atomic force microscopy (CP-AFM), correlates well with the interparticle distance, d, obtained using scattering and simulations (4, 5, 52–55). Furthermore, the periodicity, λ≈d≫a, is primarily set by the particle number density, ρ, and is relatively independent of added salt, charge at solid surfaces, and particle size, a (4, 5, 53–55). Assuming that analogy between λ∝ρ−1/3 in the nanoparticle studies and Δh∝c−1/3 in stratified foam studies arises due to similar underlying physics, Danov et al. (32) and Anachkov et al. (11) argued that Δh≈d or step size equals the intermicellar distance, d, in bulk solutions and hypothesized that step size from stratification studies could be used for determining aggregation number as Nagg≈(c−CMC)(Δh)3. However, Yilixiati et al. (17) showed that on salt addition, the measured Δh values for micellar SDS solutions do not collapse onto a single curve even if plotted against micellar number density, ρ, as micelle number and dimensions can change on the addition of salt (or surfactant) (2), whereas nanoparticle dimensions remain constant. Furthermore, solid boundaries that can impact SFA and AFM measurements are absent in stratifying foam films. However, the thickness of stratifying films is rather heterogeneous, and the average thickness changes in a stepwise fashion. Thus, the analogy between stratifying micelles in foam films and stratifying nanoparticle dispersions under confinement between solid surfaces requires further investigation. In particular, a comparison between multiple length-scales including micelle dimensions, Debye length, intermicellar distance, d and step-size, Δh, and the consequences of thickness heterogeneities within foam films are warranted.In this study, we contrast the concentration-dependent changes in step-size measured in foam stratification studies with micellar dimensions and intermicellar distances in bulk solutions obtained using SAXS for aqueous solutions of SDS. For the range of concentrations (25 mM ≤ c_SDS ≤ 250 mM) explored here, bulk rheology, interfacial tension, micelle shape and size, and interfacial charge (or potential) are nearly constant. Hence, the observed concentration-dependent changes in step-size and nanoscopic topography in stratifying films are dictated by the corresponding changes in intermicellar interactions and the resulting disjoining pressure, ΠOS(h). We visualize and analyze nanoscopic thickness variations and transitions in stratifying foam films using IDIOM (Interferometry Digital Imaging Optical Microscopy) protocols (16) (Fig. 1A) that provide requisite spatiotemporal resolution (thickness ∼1 nm, in-plane < 1 μm, time < 1 ms). We analyze SAXS data to compute micelle dimensions, volume fraction, and microstructure (order) in bulk solutions and obtain the intermicellar distance from structure factor peak in SAXS data. Finally, we discuss the ramifications of the close comparison between step size from the foam film stratification studies and micellar dimensions and intermicellar distance determined using SAXS analysis on the intermicellar interactions and the mechanistic basis of stratification.Open in a separate windowFig. 1.Schematic of the setup used for examining stratification using IDIOM protocols and illustrative examples of stepwise thinning. (A) The Scheludko-like cell contains a plane-parallel film and surrounding meniscus that emulates a single foam film and its Plateau border. The cell is placed in a closed container and stratification is visualized using reflected light microscopy. A finite volume of fluid is inserted into the cell using the side-arm connected to a syringe. No liquid is added or withdrawn during the stratification experiment, and drainage from the film into the meniscus occurs freely and spontaneously. (B) Spatiotemporal variation in interference intensity I(x, y, t; λ) is used for computing thickness transitions and variations in stratifying films. (C) Average film thickness plotted as a function of time shows stepwise thinning for foam films made with aqueous SDS solutions. The spikes and dips in thickness plots appear when mesas or domains emerge in the region selected for computing average thickness. The data are shifted horizontally for clarity.     

Temporal trends of organochlorine concentrations in umbilical cord blood of newborns from the lower north shore of the St. Lawrence river (Québec,Canada)

This study describes the time trends of organochlorines [OCs; 14 polychlorinated biphenyls (PCBs) and 11 chlorinated pesticides] in umbilical cord plasma of newborns in a remote Canadian coastal population. We analyzed 408 cord blood samples collected between 1993 and 2000 for PCBs, chlordanes, dichlorodiphenyltrichloroethane (DDT), dichlorodiphenyltrichloroethylene (DDE), hexachlorobenzene (HCB), and n-3 fatty acids. We also gathered information on the mothers (age, past and present residence, ethnic group, use of tobacco during pregnancy, and breast-feeding during previous pregnancies). From 1993 to 2000, mean concentrations of PCBs, chlordanes, DDT/DDE, and HCB in cord blood decreased by 63%, 25%, 66%, and 69%, respectively (p < 0.0001). Multiple regression analysis with the year of birth as the main independent variable yielded a strong significant exponential decrease for all contaminants (in all age and ethnic groups). We detected no monthly or seasonal pattern. We used n-3 fatty acids concentration as a surrogate of maternal fish consumption. Fish consumption declined only slightly between 1993 and 2000, but this decrease did not contribute significantly to the reduction of OCs. These results show that prenatal exposure to persistent OCs has declined significantly between 1993 and 2000 in this population.     

Multicenter phase II study of brequinar sodium in patients with advanced lung cancer

Summary A total of 53 patients with advanced lung cancer [non-small-cell (NSC), 21; small-cell (SC), 32] were treated with brequinar sodium. All of the NSC patients were chemotherapy-naive, but 31/32 (97%) SC patients had failed a multiagent chemotherapy program prior to study entry. Brequinar was given intravenously at a median weekly dose of 1200 mg/m². The toxicity was moderate, with 19 patients (36%) experiencing grade 3 or 4 toxicity. Objective responses were observed in one NSC and two SC patients. We conclude that at this dose and on this schedule, brequinar does not have sufficient activity in patients with NSC or in patients with previously treated SC to warrant further evaluation. However, since responses were observed in previously treated SC lung-cancer patients, further evaluation in chemotherapy-naive patients may be warranted.This study was supported by The DuPont Pharmaceutical Co., Wilmington, Delaware