Enhancing validity, reliability and participation in self-reported health outcome measurement for children and young people: a systematic review of recall period, response scale format, and administration modality.

INTRODUCTION: Self-report is the gold standard for measuring children's health-related outcomes. Design of such measures is complex and challenging. This review aims to systematically appraise the evidence on recall period, response scale format, mode of administration and approaches needed to enable children and young people < 19 years to participate in valid and reliable self-reporting of their health outcomes. METHOD: PsycInfo, Medline, CINAHL and Embase were searched from 1 January 1990 to 15 March 2020, and citation searching undertaken in Scopus. Articles were included if they were primary research or case reports of ≥ 3 participants reporting the following: recall period, response scale selection, administration modality. Quality was assessed using QualSyst, and results synthesised narratively. This review was conducted and reported according to PRISMA guidelines. RESULTS: 81 of 13,215 retrieved articles met the inclusion criteria. Children < 5 years old cannot validly and reliably self-report health outcomes. Face scales demonstrate better psychometric properties than visual analogue or Likert scales. Computerised and paper scales generally show equivalent construct validity. Children prefer computerised measures. Children ≤ 7 years old think dichotomously so need two response options. Those > 8 years old can reliably use a 3-point scale. CONCLUSION: The results of this review have both clinical and research implications. They can be used to inform appropriate choice of PROM for use with CYP in the clinical setting. We also give eight recommendations for future development of self-reported outcome measures for children and young people.

Nonlinear Ultrafast Spin Scattering in the Skyrmion Phase of Cu_{2}OSeO_{3}.

Ultrafast x-ray scattering studies of the topological Skyrmion phase in Cu_{2}OSeO_{3} show the dynamics to be strongly dependent on the excitation energy and fluence. At high photon energies, where the electron-spin scattering cross section is relatively high, the excitation of the topological Skyrmion phase shows a nonlinear dependence on the excitation fluence, in contrast to the excitation of the conical phase which is linearly dependent on the excitation fluence. The excitation of the Skyrmion order parameter is nonlinear in the magnetic excitation resulting from scattering during electron-hole recombination, indicating different dominant scattering processes in the conical and Skyrmion phases.

Coupled Skyrmion sublattices in Cu(2)OSeO(3).

We report the observation of a Skyrmion lattice in the chiral multiferroic insulator Cu2OSeO3 using Cu L3-edge resonant soft x-ray diffraction. We observe the unexpected existence of two distinct Skyrmion sublattices that arise from inequivalent Cu sites with chemically identical coordination numbers but different magnetically active orbitals. The Skyrmion sublattices are rotated with respect to each other, implying a long wavelength modulation of the lattice. The modulation vector is controlled with an applied magnetic field, associating this moirélike phase with a continuous phase transition. Our findings will open up a new class of science involving manipulation of quantum topological states.

Real-time manifestation of strongly coupled spin and charge order parameters in stripe-ordered La(1.75)Sr(0.25)NiO(4) nickelate crystals using time-resolved resonant x-ray diffraction.

We investigate the order parameter dynamics of the stripe-ordered nickelate, La(1.75)Sr(0.25)NiO(4), using time-resolved resonant x-ray diffraction. In spite of distinct spin and charge energy scales, the two order parameters' amplitude dynamics are found to be linked together due to strong coupling. Additionally, the vector nature of the spin sector introduces a longer reorientation time scale which is absent in the charge sector. These findings demonstrate that the correlation linking the symmetry-broken states does not unbind during the nonequilibrium process, and the time scales are not necessarily associated with the characteristic energy scales of individual degrees of freedom.

Ferromagnetic enhancement of CE-type spin ordering in (Pr,Ca)MnO3.

We present resonant soft x-ray scattering results from small bandwidth manganites (Pr,Ca)MnO(3), which show that the CE-type spin ordering (SO) at the phase boundary is stabilized only below the canted antiferromagnetic transition temperature and enhanced by ferromagnetism in the macroscopically insulating state (FM-I). Our results reveal the fragility of the CE-type ordering that underpins the colossal magnetoresistance effect in this system, as well as an unexpected cooperative interplay between FM-I and CE-type SO which is in contrast to the competitive interplay between the ferromagnetic metallic state and CE-type ordering.

Pruritus measurement and treatment.

Pruritus measurement is problematic, because of its subjective nature and poor localization. Ratio scales enhance the usefulness of the visual analogue scale (VAS) by reducing variation; other scales such as the generalized labelled magnitude scale may also be useful. Pruritus neuroanatomy includes peripheral receptors, peripheral and central nerves, ascending and descending spinal pathways, and several brain regions. Pruritus receptors include Merkel discs and free nerve endings, and itch receptors have fast or slow adaptation. In this review, we discuss the pathophysiology of pruritus in atopic dermatitis, psoriasis and scabies. Pruritus treatment is reviewed for topical agents and antihistamines. Future research directions are suggested.

Many common drugs in dermatology are light, temperature, or moisture-sensitive.

Photosensitivity is defined as responsiveness to light exposure. For many common dermatologic drugs, proper storage conditions are essential for maintaining drug activity. Degradation and loss of activity can occur with exposure to light, temperature, and/ or moisture. For example, ketoconazole degrades after 24 hours of light exposure. In this article storage guidelines for common dermatology drugs are provided. We suspect that drug degradation is common due to improper storage and that improved patient instruction regarding storage will reduce degradation and alleviate some of the danger associated with improper storage and usage patterns.

Molecular interpretation of fluorescence solvent relaxation of Patman and 2H NMR experiments in phosphatidylcholine bilayers.

The analysis of time-dependent fluorescence shifts of the bilayer probe 6-hexadecanoyl-2-(((2-(trimethylammonium)ethyl)methyl)amino)naphthalene chloride (Patman) offers valuable information on the hydration and dynamics of phospholipid headgroups. Quenching studies on vesicles composed of four phosphatidylcholines with different hydrocarbon chains (18:1c9/18:1c9, DOPC; 16:0/18:1c9, POPC; 18:1c9/16:0, OPPC; 18:1c6/18:1c6, PCDelta6) show that the chromophore of Patman is defined located at the level of the sn-1 ester-group in the phospholipid, which is invariant to the hydrocarbon chain. The so-called solvent relaxation (SR) approach as well as solid-state 2H NMR reveals that DOPC and PCDelta6 are more hydrated than POPC and OPPC. A strong dependence of SR kinetics on the position of double bond in the investigated fatty acid chains was observed. Apparently, the closer the double bond is located to the hydrated sn-1 ester-group, the more mobile this group becomes. This work demonstrates that the SR approach can report mobility changes within phospholipid bilayers with a remarkable molecular resolution.

Effect of free fatty acids on the permeability of 1,2-dimyristoyl-sn-glycero-3-phosphocholine bilayer at the main phase transition.

We measured the influence of saturated and unsaturated free fatty acids on the permeability and partition of ions into 1, 2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) bilayers. The bilayer permeability was measured using the depletion of N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-1, 2-dihexadecanoyl-sn-glycero-3-phosphatidylethanolamine (N-NBD-PE) fluorescence as a result of its reduction by dithionite. We observed a distinct increase of dithionite permeability at the main gel-fluid phase transition of DMPC. When vesicles were formed from a mixture of DMPC and oleic acid, the membrane permeability at the phase transition was reduced drastically. Stearic acid and methyl ester of oleic acid have little effect. Similar results in the quenching of pyrene-PC in DMPC vesicles by iodide were obtained. Again, the increase of iodide partition into the lipid phase at the main phase transition of DMPC was abolished by the addition of unsaturated free fatty acids. Free fatty acids, in concentrations up to 5 mol%, do not abolish DMPC phase transition when measured by differential scanning calorimetry. It seems that unsaturated, but not saturated, free fatty acids reduce the lipid bilayer permeability to dithionite and iodide ions at the main phase transition of DMPC, without altering the thermodynamic properties of the bilayer.

Merocyanine interaction with phosphatidylcholine bilayers.

Merocyanine (MC 540) is a fluorescent probe whose optical properties depend on the environmental polarity. In the presence of lipid bilayers, MC 540 binds to the membrane surface while simultaneously changing its fluorescence properties. Previous studies have shown that the fluorescence of merocyanine depends upon the lipid packing in the membrane. We measured the partitioning of MC 540 and its fluorescence properties in the presence of phosphatidylcholine membranes. We found that the fluorescence of MC 540 shows, as expected, a major change around the main phase transition of phosphatidylcholine membranes. However, instead of a step-like increase of fluorescence, the maximum at phase transition was observed. We were able to explain our data by combining two effects; dependence of MC 540 fluorescence on temperature and lipid fluidity. In addition, we established that the increase of the fluorescence intensity in the presence of lipid bilayers in the fluid state is due to the elevated partitioning of the probe into the lipid phase. The partition of MC 540 into the fluid membrane does not depends on the dye concentration in the aqueous phase. When lipid was in the gel phase the partitioning of the dye increased with its bulk concentration, whereas the fluorescence intensity remained unchanged. We conclude, therefore, that MC 540 forms nonfluorescent complexes when in the gel lipid membrane.

Merocyanine 540 as a fluorescence indicator for molecular packing stress at the onset of lamellar-hexagonal transition of phosphatidylethanolamine bilayers.

The fluorescence of Merocyanine 540 (MC 540) is sensitive to the molecular packing of membrane lipids. Therefore, the fluorescence of MC 540 is expected to be sensitive to the curvature-related packing stress at the onset of the lamellar-hexagonal phase transition. We measured the fluorescence intensity of MC 540 when the temperatures of lipid bilayers approached their lamellar-hexagonal phase transitions. The fluorescence of MC 540 in the presence of egg and dioleoylphosphatidylethanolamine bilayers increased at the respective lamellar-hexagonal phase transitions of these lipids. Furthermore, increases in fluorescence intensity were also observed at temperatures just below their phase transitions. The enhanced fluorescence was not due to the specific interaction of the dye with the ethanolamine headgroup, because no such increase was observed when the probe was exposed to phosphatidylethanolamines which do not form hexagonal phase within the range of applied temperature. In addition, when the temperature of the lamellar-hexagonal phase transition was shifted, by the addition of a small amount of phosphatidylcholine, the dependence of the fluorescence intensity on temperature was modified accordingly. We postulate that the change of MC 540 fluorescence intensity at temperatures approaching the lamellar-hexagonal phase transition reflects changes in the partition of MC 540 into the fluid lipid phase. The change in partition is influenced by the curvature stress in bilayers at temperatures just below the lamellar-hexagonal phase transition.

Interaction of free fatty acids with phospholipid bilayers.

The partition of free fatty acids (FFA) to egg-phosphatidylcholine (egg-PC) and egg-phosphatidylethanolamine (egg-PE) vesicles was studied. Upon the addition of FFA to the suspension of vesicles, the pH of the aqueous phase changed depending on the length and saturation of the FFA hydrocarbon chain, as well as on the vesicle composition. The medium pH decreased faster if FFA was added to egg-PE as compared to egg-PC vesicles. The fluorescent free fatty acid indicator (ADIFAB) was used to measure the amount of FFA remaining in the aqueous phase. Most of the FFA added to the suspension of egg-PE vesicles remained in the aqueous phase, whereas in the presence of egg-PC vesicles the FFA partitioned preferentially into the lipid phase. The amount of FFA incorporated into the lipid bilayers was estimated by measuring the changes of pH at the lipid bilayer surface, using fluorescein-PE. At high surface concentrations of FFA, decreasing pH at the bilayer surface caused the protonation of FFA, and raised the pK of FFA at the bilayer surface from 5 to about 7. The partition of FFA in egg-PE vesicles was an order of magnitude lower than that in egg-PC vesicles. The incorporation amount was determined more by the molecular packing than by the nature of lipid headgroups, because steroylcaprioyl-PE, which preferred the bilayer structure, behaved more like egg-PC than egg-PE. Understanding FFA partition characteristics would help to interpret the hydrolysis measurements of phospholipids, and to explain many biological activities of FFA.

ESR and monolayer study of the localization of coenzyme Q10 in artificial membranes.

The data obtained from the ESR experiments show a complex, depth dependent effect of CoQ10 on the lipid molecules mobility in the bilayer. These effects depend both on its concentration and the temperature. CoQ10 disturbs not only the hydrophobic core of the membrane but also the region close to the hydrophilic headgroups of phospholipids. Both these effects could be explained by the fact that the high hydrophobicity of CoQ10 causes the molecules to position itself in the interior of the bilayer, but at the same time its water seeking headgroup is located close to the region of the polar headgrops of membrane lipids. The presence of CoQ10 in the hydrophobic core has further implications on the properties of membrane intrinsic domain. Results of monolayer experiments indicate that CoQ10 may form aggregates when mixed with PC molecules in the lipid hydrocarbon chain-length dependent manner. CoQ10 is not fully miscible with DMPC or DPPC but it is well miscible with the long-chain DSPC molecules. Our suggestion is that CoQ10 when present in long-chain phospholipid bilayer, interacts with saturated fatty acyl-chains and adapt the structure which allows such interactions: either parallel to the saturated acyl chains or "pseudo-ring" conformation resembling sterol structure.

Selective interlayer ferromagnetic coupling between the Cu spins in YBa2Cu3O7-x grown on top of La0.7Ca0.3MnO3.

Studies to date on ferromagnet/d-wave superconductor heterostructures focus mainly on the effects at or near the interfaces while the response of bulk properties to heterostructuring is overlooked. Here we use resonant soft x-ray scattering spectroscopy to reveal a novel c-axis ferromagnetic coupling between the in-plane Cu spins in YBa2Cu3O7-x (YBCO) superconductor when it is grown on top of ferromagnetic La0.7Ca0.3MnO3 (LCMO) manganite layer. This coupling, present in both normal and superconducting states of YBCO, is sensitive to the interfacial termination such that it is only observed in bilayers with MnO2 but not with La0.7Ca0.3O interfacial termination. Such contrasting behaviors, we propose, are due to distinct energetic of CuO chain and CuO2 plane at the La0.7Ca0.3O and MnO2 terminated interfaces respectively, therefore influencing the transfer of spin-polarized electrons from manganite to cuprate differently. Our findings suggest that the superconducting/ferromagnetic bilayers with proper interfacial engineering can be good candidates for searching the theorized Fulde-Ferrel-Larkin-Ovchinnikov (FFLO) state in cuprates and studying the competing quantum orders in highly correlated electron systems.

Modification of some properties of spherical lipid membranes induced by the association with fructose-1,6-bisphosphate aldolase.

The influence of fructose-1,6-bisphosphate aldolase, as a membrane peripheral protein, on some electrical and transport properties of spherical lipid membranes was investigated. It was found that the association of the enzyme with the membrane did not effect markedly the electrical conductance or capacity of the membrane but decreased the water filtration coefficient and the cationic transferance number. The enzyme association also modifies temperature characteristics of the membrane parameters.

Relationship between membrane lipid mobility and spectrin distribution in lymphocytes.

We have previously established that T and B lymphocytes in situ are remarkably heterogeneous with respect to the cytoskeletal protein spectrin. Since in erythrocytes spectrin is known to play an important role in the regulation of membrane fluidity, lipid organization and lateral mobility of membrane proteins, we have sought to determine if the heterogeneous patterns of spectrin distribution that we have observed are related to possible differences in membrane lipid organization in these various subsets. To this end, we have utilized a fluorescent pyrene-labelled phospholipid as a probe of the lipid lateral mobility and have examined two related T cell systems maintained in vitro, DO.11.10 cells and a spontaneously arising variant, DO.11.10V. In these (and other cloned in vitro systems) we have previously observed that the cells homogeneously express one of the kinds of spectrin distribution patterns observed in situ. Thus the uniformity of staining of these systems permits us to address whether the various patterns of spectrin distribution may be predictive of differences in membrane lipid properties. Here we show that in cells in which there is little or nor spectrin at the plasma membrane (DO.11.10) that the lipids in the plasma membrane are considerably less mobile than in its related variant in which spectrin is diffusely distributed within the cell and at the plasma membrane. From this and previous results, we conclude that differences in the distribution of the cytoskeletal protein spectrin among lymphocytes may be a useful parameter in helping to predict the status of membrane lipid organization.

The electrostatics of lipid surfaces.

Charged lipids constitute a substantial fraction of all membrane lipids. Their charges vary in quantity and distribution within their headgroup regions. In long range interactions, their charges' value and electrostatic potential in the vicinity of the membrane surface can be approximated by the Guy-Chapman theory. This theory treats the interface as a charged structureless plain surrounded by uniform environments. However, if one considers intermolecular interactions, such assumptions need to be revised. The interface is in reality a thick region containing the residual charges of lipid headgroups. Their arrangement depends on the type of lipid present in the membrane. The variety of lipids and their biological functions suggests that charge distribution determines the extent and type of interaction with surface associated molecules. Numerous examples show that protein behavior at the lipid bilayer surface is determined by the type of lipid present, indicating protein specificity towards certain surface locations and local properties (determined by lipid composition) of a particular type. Such specificity is achieved by a combination of electrostatic, hydrophobic and enthropic effects. Comparing lipid biological activity, it can be stated that residual charge distribution is one of the factors of intermolecular recognition leading to the specific interaction of lipid molecules and selected proteins in various processes, particularly those involved with signal transduction pathways. Such specificity enables a variety of processes occurring simultaneously on the same membrane surface to function without cross-reaction interference.

Iodide penetration into lipid bilayers as a probe of membrane lipid organization.

The quenching efficiency of iodide as a penetrating fluorescence quencher for a membrane-associated fluorophore was utilized to measure the molecular packing of lipid bilayers. The KI quenching efficiency of tryptophan-fluorescence from melittin incorporated in DMPC bilayer vesicles peaks at the phase transition temperature (24 degrees C) of DMPC, whereas acrylamide quenching efficiency does not depend on temperature. The ability of iodide to penetrate the hydrocarbon region of the bilayer was examined by measuring the fluorescence quenching of the pyrene-phosphatidylcholine incorporated into DMPC vesicles (pyrene was attached to the 10th carbon of the sn-2 chain). The quenching efficiency of pyrene by iodide again shows a maximum at the lipid phase transition. We conclude that iodide penetrates the membrane hydrocarbon region at phase transition through an increased number of bilayer defects. The magnitude of change in quenching efficiency of iodide during lipid phase transition provides a sensitive technique to probe the lipid organization in membranes.

Dithionite penetration through phospholipid bilayers as a measure of defects in lipid molecular packing.

The permeability of dithionite through bilayers was utilized to probe the structural defects in the bilayers of these lipids through their respective gel-fluid and bilayer-hexagonal phase transitions. The water soluble dithionite ion penetrates intact bilayers very slowly. The rate of irreversible quenching of the fluorescence of NBD-PE labelled liposomes may thus be used as an indicator of the permeability of this ion through bilayers. The quenching rate has a fast and a slow component, the fast one corresponds to the quenching of fluorophores immediately accessible to the quencher, i.e. those on the outer surface of liposomes. The slower component represents the average rate of penetration of the quencher through the bilayer, to quench those fluorophores at the inner shells of the multilamellar vesicles. Both rates may be approximated by a single exponential function. The slow exponent is simply related to the permeability. The permeability of DMPC as a function of temperature shows a peak at the gel-fluid phase transition at 24 degrees C, but returns to about the pre-transition value at temperatures above the phase transition. The permeability of egg PE shows a hump at 45 degrees C before the hexagonal phase transition at 65 degrees C is reached and becomes infinite at the hexagonal phase transition as all fluorophores are immediately accessible to the quencher. We believe that the permeability measured by this method relates more to the molecular packing defects which maximizes at the gel-fluid phase transition temperatures just below the bilayer-hexagonal phase transition, rather than the general packing order which simply changes with structural phases.

Dietary fatty acids alter the adhesion properties of lymphocytes to extracellular matrix proteins.

Dietary fats have been shown by many investigators to affect immune responses in vitro and in vivo. However, the exact mechanism(s) by which fats or their metabolic derivatives affect immune function is still unknown. In this report we have investigated whether short-term in vitro exposure to fatty acids alters the adhesion of lymphocytes to extracellular matrix proteins. We found remarkably heterogeneous effects with these agents on lymphocyte adhesion; increases and decreases in adhesion were observed depending upon the fatty acid, cell type and extracellular matrix protein used. Alterations in the adhesion potential of lymphocytes could serve as a mechanism for the reported effects of fatty acids on immune function since lymphocytes are dependent upon rapid and reversible adherence events for most of their effector activities.