The use of bootstrap methods for analysing health-related quality of life outcomes (particularly the SF-36)

Health-Related Quality of Life (HRQoL) measures are becoming increasingly used in clinical trials as primary outcome measures. Investigators are now asking statisticians for advice on how to analyse studies that have used HRQoL outcomes. HRQoL outcomes, like the SF-36, are usually measured on an ordinal scale. However, most investigators assume that there exists an underlying continuous latent variable that measures HRQoL, and that the actual measured outcomes (the ordered categories), reflect contiguous intervals along this continuum. The ordinal scaling of HRQoL measures means they tend to generate data that have discrete, bounded and skewed distributions. Thus, standard methods of analysis such as the t-test and linear regression that assume Normality and constant variance may not be appropriate. For this reason, conventional statistical advice would suggest that non-parametric methods be used to analyse HRQoL data. The bootstrap is one such computer intensive non-parametric method for analysing data. We used the bootstrap for hypothesis testing and the estimation of standard errors and confidence intervals for parameters, in four datasets (which illustrate the different aspects of study design). We then compared and contrasted the bootstrap with standard methods of analysing HRQoL outcomes. The standard methods included t-tests, linear regression, summary measures and General Linear Models. Overall, in the datasets we studied, using the SF-36 outcome, bootstrap methods produce results similar to conventional statistical methods. This is likely because the t-test and linear regression are robust to the violations of assumptions that HRQoL data are likely to cause (i.e. non-Normality). While particular to our datasets, these findings are likely to generalise to other HRQoL outcomes, which have discrete, bounded and skewed distributions. Future research with other HRQoL outcome measures, interventions and populations, is required to confirm this conclusion

Direct visualization of electroporation-assisted in vivo gene delivery to tumors using intravital microscopy – spatial and time dependent distribution

Background Electroporation is currently receiving much attention as a way to increase drug and DNA delivery. Recent studies demonstrated the feasibility of electrogene therapy using a range of therapeutic genes for the treatment of experimental tumors. However, the transfection efficiency of electroporation-assisted DNA delivery is still low compared to viral methods and there is a clear need to optimize this approach. In order to optimize treatment, knowledge about spatial and time dependency of gene expression following delivery is of utmost importance in order to improve gene delivery. Intravital microscopy of tumors growing in dorsal skin fold window chambers is a useful method for monitoring gene transfection, since it allows non-invasive dynamic monitoring of gene expression in tumors in a live animal. Methods Intravital microscopy was used to monitor real time spatial distribution of the green fluorescent protein (GFP) and time dependence of transfection efficiency in syngeneic P22 rat tumor model. DNA alone, liposome-DNA complexes and electroporation-assisted DNA delivery using two different sets of electric pulse parameters were compared. Results Electroporation-assisted DNA delivery using 8 pulses, 600 V/cm, 5 ms, 1 Hz was superior to other methods and resulted in 22% increase in fluorescence intensity in the tumors up to 6 days post-transfection, compared to the non-transfected area in granulation tissue. Functional GFP was detected within 5 h after transfection. Cells expressing GFP were detected throughout the tumor, but not in the surrounding tissue that was not exposed to electric pulses. Conclusions Intravital microscopy was demonstrated to be a suitable method for monitoring time and spatial distribution of gene expression in experimental tumors and provided evidence that electroporation-assisted gene delivery using 8 pulses, 600 V/cm, 5 ms, 1 Hz is an effective method, resulting in early onset and homogenous distribution of gene expression in the syngeneic P22 rat tumor model

Reflex responses from the main pulmonary artery and bifurcation in anaesthetised dogs

This study was undertaken to determine the reflex cardiovascular and respiratory responses to discrete stimulation of pulmonary arterial baroreceptors using a preparation in which secondary modulation of responses from other reflexes was prevented. Dogs were anaesthetised with [alpha]-chloralose, artificially ventilated, the chests widely opened and a cardiopulmonary bypass established. The main pulmonary arterial trunk, bifurcation and extrapulmonary arteries as far as the first lobar arteries on each side were vascularly isolated and perfused through the left pulmonary artery and drained via the right artery through a Starling resistance which controlled pulmonary arterial pressure. Pressures distending systemic baroreceptors and reflexogenic regions in the heart were controlled. Reflex vascular responses were assessed from changes in perfusion pressures to a vascularly isolated hind limb and to the remainder of the subdiaphragmatic systemic circulation, both of which were perfused at constant flows. Respiratory responses were assessed from recordings of efferent phrenic nerve activity. Increases in pulmonary arterial pressure consistently evoked increases in both perfusion pressures and in phrenic nerve activity. Both vascular and respiratory responses were obtained when pulmonary arterial pressure was increased to above about 30 mmHg. Responses increased at higher levels of pulmonary arterial pressures. In 13 dogs increases in pulmonary arterial pressure to 45 mmHg increased systemic perfusion pressure by 24 ± 7 mmHg (mean ± S.E.M.) from 162 ± 11 mmHg. Setting carotid sinus pressure at different levels did not influence the vascular response to changes in pulmonary arterial pressure. The presence of a negative intrathoracic pressure of -20 mmHg resulted in larger vascular responses being obtained at lower levels of pulmonary arterial pressure. This indicates that the reflex may be more effective in the intact closed-chest animal. These results demonstrate that stimulation of pulmonary arterial baroreceptors evokes a pressor reflex and augments respiratory drive. This reflex is likely to be elicited in circumstances where pulmonary arterial pressure increases and the negative excursions of intrathoracic pressure become greater. They are likely, therefore, to be involved in the cardio-respiratory response to exercise as well as in pathological states such as pulmonary hypertension or restrictive or obstructive lung disease

Factors influencing agreement between child self-report and parent proxy-reports on the Pediatric Quality of Life Inventory™ 4.0 (PedsQL™) generic core scales

BACKGROUND In situations where children are unable or unwilling to respond for themselves, measurement of quality of life (QOL) is often obtained by parent proxy-report. However the relationship between child self and parent proxy-reports has been shown to be poor in some circumstances. Additionally the most appropriate statistical method for comparing ratings between child and parent proxy-reports has not been clearly established. The objectives of this study were to assess the: 1) agreement between child and parent proxy-reports on an established child QOL measure (the PedsQL™) using two different statistical methods; 2) effect of chronological age and domain type on agreement between children's and parents' reports on the PedsQL™; 3) relationship between parents' own well-being and their ratings of their child's QOL. METHODS One hundred and forty-nine healthy children (5.5 – 6.5, 6.5 – 7.5, and 7.5 – 8.5 years) completed the PedsQL™. One hundred and three of their parents completed these measures in relation to their child, and a measure of their own QOL (SF-36). RESULTS Consistency between child and parent proxy-reports on the PedsQL™ was low, with Intra-Class correlation coefficients ranging from 0.02 to 0.23. Correlations were higher for the oldest age group for Total Score and Psychosocial Health domains, and for the Physical Health domain in the youngest age group. Statistically significant median differences were found between child and parent-reports on all subscales of the PedsQL™. The largest median differences were found for the two older age groups. Statistically significant correlations were found between parents' own QOL and their proxy-reports of child QOL across the total sample and within the middle age group. CONCLUSION Intra-Class correlation coefficients and median difference testing can provide different information on the relationship between parent proxy-reports and child self-reports. Our findings suggest that differences in the levels of parent-child agreement previously reported may be an artefact of the statistical method used. In addition, levels of agreement can be affected by child age, domains investigated, and parents' own QOL. Further studies are needed to establish the optimal predictors of levels of parent-child agreement

Using correlation matrix memories for inferencing in expert systems

Outline of The Chapter… Section 16.2 describes CMM and the Dynamic Variable Binding Problem. Section 16.3 deals with how CMM is used as part of an inferencing engine. Section 16.4 details the important performance characteristics of CMM

Spin and orbital moments of ultra-thin Fe films on various semiconductor surfaces

The magnetic moments of ultrathin Fe films on three different III-V semiconductor substrates, namely GaAs, InAs and In0.2Ga0.8As have been measured with X-ray magnetic circular dichroism at room temperature to assess their relative merits as combinations suitable for next-generation spintronic devices. The results revealed rather similar spin moments and orbital moments for the three systems, suggesting the relationship between film and semiconductor lattice parameters to be less critical to magnetic moments than magnetic anisotropy

Interface magnetic properties of epitaxial Fe-InAs heterostructures

The growth and interface magnetic properties of epitaxial Fe films grown on InAs (100)-4 x 2 have been studied using low-energy electron diffraction, in situ magneto-optical Kerr effect, and X-ray magnetic circular dichronism. The magnetic properties at room temperature were found to proceed via three phases with thickness; a nonmagnetic phase, a superparamagnetic phase, and a ferromagnetic phase. The initial ferromagnetic phase might be stabilized by interparticle interactions. The films show bulk-like spin moments of 1.90+/-0.15 mu(B) with the thickness above about 20 ML and a large enhancement similar to 260% of the ratio of orbital versus spin moment in the ultrathin region

The role of interfaces in CoFe/IrMn exchange biased systems

A trilayer system consisting of an IrMn layer exchanged coupled to two CoFe layers of equal thickness has been studied. A single stage reversal was observed over a wide range of temperatures. Two bilayers with the same thicknesses of the pinning layer but different ferromagnetic thicknesses were also studied. By comparing the magnetic properties of these three stacks the effect of the interfacial area on the exchange field and the coercivity has been determined. We find that the interfacial area has a very minor effect on the exchange field H-ex and the blocking temperature (T-B) but causes a doubling of the coercivity (H-c). This indicates that H-c is dominated by the interface whereas the exchange bias is controlled by volumetric effects

A model for deformable roll coating with negative gaps and incompressible compliant layers

A soft elastohydrodynamic lubrication model is formulated for deformable roll coating involving two contra-rotating rolls, one rigid and the other covered with a compliant layer. Included is a finite-strip model (FSM) for the deformation of the layer and a lubrication model with suitable boundary conditions for the motion of the fluid. The scope of the analysis is restricted to Newtonian fluids, linear elasticity/viscoelasticity and equal roll speeds, with application to the industrially relevant highly loaded or 'negative gap' regime. Predictions are presented for coated film thickness, interroll thickness, meniscus location, pressure and layer deformation as the control parameters - load (gap), elasticity, layer thickness and capillary number, Ca - are varied. There are four main results: (i) Hookean spring models are shown to be unable to model effectively the deformation of a compliant layer when Poisson's ratio nu --> 0.5. In particular, they fall to predict the swelling of the layer at the edge of the contact region which increases as v - 0.5; they also fail to locate accurately the position of the meniscus, X-M, and to identify the presence, close to the meniscus, of a 'nib' (constriction in gap thickness) and associated magnification of the sub-ambient pressure loop. (ii) Scaling arguments suggest that layer thickness and elasticity may have similar effects on the field variables. It is shown that for positive gaps this is true, whereas for negative gaps they have similar effects on the pressure profile and flow rate yet quite different effects on layer swelling (deformation at the edge of the contact region) and different effects on X-M. (iii) For negative gaps and Ca similar to O(1), the effect of varying either viscosity or speed and hence Ca is to significantly alter both the coating thickness and X-M. This is contrary to the case of fixed-gap rigid roll coating. (iv) Comparison between theoretical predictions and experimental data shows quantitive agreement in the case of X-M and qualitive agreement for flow rate. It is shown that this difference in the latter case may be due to viscoelastic effects in the compliant layer

A parallel domain decomposition algorithm for the adaptive finite element solution of 3-D convection-diffusion problems

In this paper we extend our previous work on the use of domain decomposition (DD) preconditioning for the parallel finite element (FE) solution of three-dimensional elliptic problems [3,6] and convection-dominated problems [7,8] to include the use of local mesh refinement. The preconditioner that we use is based upon a hierarchical finite element mesh that is partitioned at the coarsest level. The individual subdomain problems are then solved on meshes that have a single layer of overlap at each level of refinement in the mesh. Results are presented to demonstrate that this preconditioner leads to iteration counts that appear to be independent of the level of refinement in the final mesh,even in the case where this refinement is local in nature: as produced by an adaptive finite element solver for example