4,386 research outputs found
Multiple Imputation of Missing Composite Outcomes in Longitudinal Data.
In longitudinal randomised trials and observational studies within a medical context, a composite outcome-which is a function of several individual patient-specific outcomes-may be felt to best represent the outcome of interest. As in other contexts, missing data on patient outcome, due to patient drop-out or for other reasons, may pose a problem. Multiple imputation is a widely used method for handling missing data, but its use for composite outcomes has been seldom discussed. Whilst standard multiple imputation methodology can be used directly for the composite outcome, the distribution of a composite outcome may be of a complicated form and perhaps not amenable to statistical modelling. We compare direct multiple imputation of a composite outcome with separate imputation of the components of a composite outcome. We consider two imputation approaches. One approach involves modelling each component of a composite outcome using standard likelihood-based models. The other approach is to use linear increments methods. A linear increments approach can provide an appealing alternative as assumptions concerning both the missingness structure within the data and the imputation models are different from the standard likelihood-based approach. We compare both approaches using simulation studies and data from a randomised trial on early rheumatoid arthritis patients. Results suggest that both approaches are comparable and that for each, separate imputation offers some improvement on the direct imputation of a composite outcome
Novel critical point drying (CPD) based preparation and transmission electron microscopy (TEM) imaging of protein specific molecularly imprinted polymers (HydroMIPs)
We report the transmission electron microscopy (TEM) imaging of a hydrogel-based molecularly imprinted polymer (HydroMIP) specific to the template molecule bovine haemoglobin (BHb). A novel critical point drying based sample preparation technique was employed to prepare the molecularly imprinted polymer (MIP) samples in a manner that would facilitate the use of TEM to image the imprinted cavities, and provide an appropriate degree of both magnification and resolution to image polymer architecture in the <10 nm range. For the first time, polymer structure has been detailed that clearly displays molecularly imprinted cavities, ranging from 5-50 nm in size, that correlate (in terms of size) with the protein molecule employed as the imprinting template. The modified critical point drying sample preparation technique used may potentially play a key role in the imaging of all molecularly imprinted polymers, particularly those prepared in the aqueous phase
Scallop swimming kinematics and muscle performance: modelling the effects of "within-animal" variation in temperature sensitivity
Escape behaviour was investigated in Queen scallops (Aequipecten opercularis) acclimated to 5, 10 or 15 degrees C and tested at their acclimation temperature. Scallops are active molluscs, able to escape from predators by jet-propelled swimming using a striated muscle working in opposition to an elastic hinge ligament. The first cycle of the escape response was recorded using high-speed video ( 250 Hz) and whole-animal velocity and acceleration determined. Muscle shortening velocity, force and power output were calculated using measurements of valve movement and jet area, and a simple biomechanical model. The average shortening speed of the adductor muscle had a Q(10) of 2.04, significantly reducing the duration of the jetting phase of the cycle with increased temperature. Muscle lengthening velocity and the overall duration of the clap cycle were changed little over the range 5 - 15 degrees C, as these parameters were controlled by the relatively temperature-insensitive, hinge ligament. Improvements in the average power output of the adductor muscle over the first clap cycle ( 222 vs. 139 W kg(-1) wet mass at 15 and 5 degrees C respectively) were not translated into proportional increases in overall swimming velocity, which was only 32% higher at 15 degrees C ( 0.37m s(-1)) than 5 degrees C (0.28 m s(-1))
Bayesian Methods for Exoplanet Science
Exoplanet research is carried out at the limits of the capabilities of
current telescopes and instruments. The studied signals are weak, and often
embedded in complex systematics from instrumental, telluric, and astrophysical
sources. Combining repeated observations of periodic events, simultaneous
observations with multiple telescopes, different observation techniques, and
existing information from theory and prior research can help to disentangle the
systematics from the planetary signals, and offers synergistic advantages over
analysing observations separately. Bayesian inference provides a
self-consistent statistical framework that addresses both the necessity for
complex systematics models, and the need to combine prior information and
heterogeneous observations. This chapter offers a brief introduction to
Bayesian inference in the context of exoplanet research, with focus on time
series analysis, and finishes with an overview of a set of freely available
programming libraries.Comment: Invited revie
A biophysical model of cell adhesion mediated by immunoadhesin drugs and antibodies
A promising direction in drug development is to exploit the ability of
natural killer cells to kill antibody-labeled target cells. Monoclonal
antibodies and drugs designed to elicit this effect typically bind cell-surface
epitopes that are overexpressed on target cells but also present on other
cells. Thus it is important to understand adhesion of cells by antibodies and
similar molecules. We present an equilibrium model of such adhesion,
incorporating heterogeneity in target cell epitope density and epitope
immobility. We compare with experiments on the adhesion of Jurkat T cells to
bilayers containing the relevant natural killer cell receptor, with adhesion
mediated by the drug alefacept. We show that a model in which all target cell
epitopes are mobile and available is inconsistent with the data, suggesting
that more complex mechanisms are at work. We hypothesize that the immobile
epitope fraction may change with cell adhesion, and we find that such a model
is more consistent with the data. We also quantitatively describe the parameter
space in which binding occurs. Our results point toward mechanisms relating
epitope immobility to cell adhesion and offer insight into the activity of an
important class of drugs.Comment: 13 pages, 5 figure
Signatures of granular microstructure in dense shear flows
Granular materials react to shear stresses differently than do ordinary
fluids. Rather than deforming uniformly, materials such as dry sand or
cohesionless powders develop shear bands: narrow zones containing large
relative particle motion leaving adjacent regions essentially rigid[1,2,3,4,5].
Since shear bands mark areas of flow, material failure and energy dissipation,
they play a crucial role for many industrial, civil engineering and geophysical
processes[6]. They also appear in related contexts, such as in lubricating
fluids confined to ultra-thin molecular layers[7]. Detailed information on
motion within a shear band in a three-dimensional geometry, including the
degree of particle rotation and inter-particle slip, is lacking. Similarly,
only little is known about how properties of the individual grains - their
microstructure - affect movement in densely packed material[5]. Combining
magnetic resonance imaging, x-ray tomography, and high-speed video particle
tracking, we obtain the local steady-state particle velocity, rotation and
packing density for shear flow in a three-dimensional Couette geometry. We find
that key characteristics of the granular microstructure determine the shape of
the velocity profile.Comment: 5 pages, incl. 4 figure
Integrated multiple mediation analysis: A robustness–specificity trade-off in causal structure
Recent methodological developments in causal mediation analysis have addressed several issues regarding multiple mediators. However, these developed methods differ in their definitions of causal parameters, assumptions for identification, and interpretations of causal effects, making it unclear which method ought to be selected when investigating a given causal effect. Thus, in this study, we construct an integrated framework, which unifies all existing methodologies, as a standard for mediation analysis with multiple mediators. To clarify the relationship between existing methods, we propose four strategies for effect decomposition: two-way, partially forward, partially backward, and complete decompositions. This study reveals how the direct and indirect effects of each strategy are explicitly and correctly interpreted as path-specific effects under different causal mediation structures. In the integrated framework, we further verify the utility of the interventional analogues of direct and indirect effects, especially when natural direct and indirect effects cannot be identified or when cross-world exchangeability is invalid. Consequently, this study yields a robustness–specificity trade-off in the choice of strategies. Inverse probability weighting is considered for estimation. The four strategies are further applied to a simulation study for performance evaluation and for analyzing the Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer data set from Taiwan to investigate the causal effect of hepatitis C virus infection on mortality
Organisational participation and women - an attitude problem?
Employee participation is a dynamic and contested area of organisational behaviour, attracting continuing academic, practitioner and policy interest and debate. This chapter focuses on organisational participation and women
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