Towards Bayesian experimental design for nonlinear models that require a large number of sampling times

The use of Bayesian methodologies for solving optimal experimental design problems has increased. Many of these methods have been found to be computationally intensive for design problems that require a large number of design points. A simulation-based approach that can be used to solve optimal design problems in which one is interested in finding a large number of (near) optimal design points for a small number of design variables is presented. The approach involves the use of lower dimensional parameterisations that consist of a few design variables, which generate multiple design points. Using this approach, one simply has to search over a few design variables, rather than searching over a large number of optimal design points, thus providing substantial computational savings. The methodologies are demonstrated on four applications, including the selection of sampling times for pharmacokinetic and heat transfer studies, and involve nonlinear models. Several Bayesian design criteria are also compared and contrasted, as well as several different lower dimensional parameterisation schemes for generating the many design points.

Peer-led diabetes self-management programme for community-dwelling older people in China : study protocol for a quasi-experimental design

Aim. A protocol for a new peer-led self-management programme for communitydwelling older people with diabetes in Shanghai, China. Background. The increasing prevalence of type 2 diabetes poses major public health challenges. Appropriate education programmes could help people with diabetes to achieve self-management and better health outcomes. Providing education programmes to the fast growing number of people with diabetes present a real challenge to Chinese healthcare system, which is strained for personnel and funding shortages. Empirical literature and expert opinions suggest that peer education programmes are promising. Design. Quasi-experimental. Methods. This study is a non-equivalent control group design (protocol approved in January, 2008). A total of 190 people, with 95 participants in each group, will be recruited from two different, but similar, communities. The programme, based on Social Cognitive Theory, will consist of basic diabetes instruction and social support and self-efficacy enhancing group activities. Basic diabetes instruction sessions will be delivered by health professionals, whereas social support and self-efficacy enhancing group activities will be led by peer leaders. Outcome variables include: self-efficacy, social support, self-management behaviours, depressive status, quality of life and healthcare utilization, which will be measured at baseline, 4 and 12 weeks. Discussion. This theory-based programme tailored to Chinese patients has potential for improving diabetes self-management and subsequent health outcomes. In addition, the delivery mode, through involvement of peer leaders and existing community networks,is especially promising considering healthcare resource shortage in China.

A comparison of calculated and experimental HRTEM images of twinned boron carbide

High resolution TEM images of boron carbide (B13C2) have been recorded and compared with images calculated using the multislice method as implemented by M. A. O'Keefe in the SHRLI programs. Images calculated for the [010] zone, using machine parameters for the JEOL 2000FX AEM operating at 200 keV, indicate that for the structure model of Will et al., the optimum defocus image can be interpreted such that white spots correspond to B12 icosahedra for thin specimens and to low density channels through the structure adjacent to the direct inter-icosahedral bonds for specimens of intermediate thickness (-40 > t > -100 nm). With this information, and from the symmetry observed in the TEM images, it is likely that the (101) twin plane passes through the center of icosahedron located at the origin. This model was tested using the method of periodic continuation. Resulting images compare favorably with experimental images, thus supporting the structural model. The introduction of a (101) twin plane through the origin creates distortions to the icosahedral linkages as well as to the intra-icosahedral bonding. This increases the inequivalence of adjacent icosahedral sites along the twin plane, and thereby increases the likelihood of bipolaron hopping.

Growth of confined cancer spheroids : a combined experimental marker, critical modelling approach

A critical step in the dissemination of ovarian cancer is the formation of multicellular spheroids from cells shed from the primary tumour. The objectives of this study were to apply bioengineered three-dimensional (3D) microenvironments for culturing ovarian cancer spheroids in vitro and simultaneously to build on a mathematical model describing the growth of multicellular spheroids in these biomimetic matrices. Cancer cells derived from human epithelial ovarian carcinoma were embedded within biomimetic hydrogels of varying stiffness and grown for up to 4 weeks. Immunohistochemistry, imaging and growth analyses were used to quantify the dependence of cell proliferation and apoptosis on matrix stiffness, long-term culture and treatment with the anti-cancer drug paclitaxel. The mathematical model was formulated as a free boundary problem in which each spheroid was treated as an incompressible porous medium. The functional forms used to describe the rates of cell proliferation and apoptosis were motivated by the experimental work and predictions of the mathematical model compared with the experimental output. This work aimed to establish whether it is possible to simulate solid tumour growth on the basis of data on spheroid size, cell proliferation and cell death within these spheroids. The mathematical model predictions were in agreement with the experimental data set and simulated how the growth of cancer spheroids was influenced by mechanical and biochemical stimuli including matrix stiffness, culture duration and administration of a chemotherapeutic drug. Our computational model provides new perspectives on experimental results and has informed the design of new 3D studies of chemoresistance of multicellular cancer spheroids.

Experimental and modelling investigation of monolayer development with clustering

Standard differential equation–based models of collective cell behaviour, such as the logistic growth model, invoke a mean–field assumption which is equivalent to assuming that individuals within the population interact with each other in proportion to the average population density. Implementing such assumptions implies that the dynamics of the system are unaffected by spatial structure, such as the formation of patches or clusters within the population. Recent theoretical developments have introduced a class of models, known as moment dynamics models, which aim to account for the dynamics of individuals, pairs of individuals, triplets of individuals and so on. Such models enable us to describe the dynamics of populations with clustering, however, little progress has been made with regard to applying moment dynamics models to experimental data. Here, we report new experimental results describing the formation of a monolayer of cells using two different cell types: 3T3 fibroblast cells and MDA MB 231 breast cancer cells. Our analysis indicates that the 3T3 fibroblast cells are relatively motile and we observe that the 3T3 fibroblast monolayer forms without clustering. Alternatively, the MDA MB 231 cells are less motile and we observe that the MDA MB 231 monolayer formation is associated with significant clustering. We calibrate a moment dynamics model and a standard mean–field model to both data sets. Our results indicate that the mean–field and moment dynamics models provide similar descriptions of the 3T3 fibroblast monolayer formation whereas these two models give very different predictions for the MDA MD 231 monolayer formation. These outcomes indicate that standard mean–field models of collective cell behaviour are not always appropriate and that care ought to be exercised when implementing such a model.

Experimental investigation of the governing parameters in the electrospinning of poly(3-hydroxybutyrate) scaffolds : structural characteristics of the pores

We sought to determine the impact of electrospinning parameters on a trustworthy criterion that could evidently improve the maximum applicability of fibrous scaffolds for tissue regeneration. We used an image analysis technique to elucidate the web permeability index (WPI) by modeling the formation of electrospun scaffolds. Poly(3-hydroxybutyrate) (P3HB) scaffolds were fabricated according to predetermined conditions of levels in a Taguchi orthogonal design. The material parameters were the polymer concentration, conductivity, and volatility of the solution. The processing parameters were the applied voltage and nozzle-to-collector distance. With a law to monitor the WPI values when the polymer concentration or the applied voltage was increased, the pore interconnectivity was decreased. The quality of the jet instability altered the pore numbers, areas, and other structural characteristics, all of which determined the scaffold porosity and aperture interconnectivity. An initial drastic increase was observed in the WPI values because of the chain entanglement phenomenon above a 6 wt % P3HB content. Although the solution mixture significantly (p < 0.05) changed the scaffold architectural characteristics as a function of the solution viscosity and surface tension, it had a minor impact on the WPI values. The solution mixture gained the third place of significance, and the distance was approved as the least important factor.

Experimental and computer simulation validation of ultrasound phase interference created by lateral inhomogeneity of transit time in replica bone marrow composite models

Purpose: The measurement of broadband ultrasonic attenuation (BUA) in cancellous bone for the assessment of osteoporosis follows a parabolic-type dependence with bone volume fraction; having minima values corresponding to both entire bone and entire marrow. Langton has recently proposed that the primary BUA mechanism may be significant phase interference due to variations in propagation transit time through the test sample as detected over the phase-sensitive surface of the receive ultrasound transducer. This fundamentally simple concept assumes that the propagation of ultrasound through a complex solid : liquid composite sample such as cancellous bone may be considered by an array of parallel ‘sonic rays’. The transit time of each ray is defined by the proportion of bone and marrow propagated, being a minimum (tmin) solely through bone and a maximum (tmax) solely through marrow. A Transit Time Spectrum (TTS), ranging from tmin to tmax, may be defined describing the proportion of sonic rays having a particular transit time, effectively describing lateral inhomogeneity of transit time over the surface of the receive ultrasound transducer. Phase interference may result from interaction of ‘sonic rays’ of differing transit times. The aim of this study was to test the hypothesis that there is a dependence of phase interference upon the lateral inhomogenity of transit time by comparing experimental measurements and computer simulation predictions of ultrasound propagation through a range of relatively simplistic solid:liquid models exhibiting a range of lateral inhomogeneities. Methods: A range of test models was manufactured using acrylic and water as surrogates for bone and marrow respectively. The models varied in thickness in one dimension normal to the direction of propagation, hence exhibiting a range of transit time lateral inhomogeneities, ranging from minimal (single transit time) to maximal (wedge; ultimately the limiting case where each sonic ray has a unique transit time). For the experimental component of the study, two unfocused 1 MHz ¾” broadband diameter transducers were utilized in transmission mode; ultrasound signals were recorded for each of the models. The computer simulation was performed with Matlab, where the transit time and relative amplitude of each sonic ray was calculated. The transit time for each sonic ray was defined as the sum of transit times through acrylic and water components. The relative amplitude considered the reception area for each sonic ray along with absorption in the acrylic. To replicate phase-sensitive detection, all sonic rays were summed and the output signal plotted in comparison with the experimentally derived output signal. Results: From qualtitative and quantitative comparison of the experimental and computer simulation results, there is an extremely high degree of agreement of 94.2% to 99.0% between the two approaches, supporting the concept that propagation of an ultrasound wave, for the models considered, may be approximated by a parallel sonic ray model where the transit time of each ray is defined by the proportion of ‘bone’ and ‘marrow’. Conclusions: This combined experimental and computer simulation study has successfully demonstrated that lateral inhomogeneity of transit time has significant potential for phase interference to occur if a phase-sensitive ultrasound receive transducer is implemented as in most commercial ultrasound bone analysis devices.

Towards a capabilities database to inform inclusive design : Experimental investigation of effective survey-based predictors of human-product interaction

A key issue in the field of inclusive design is the ability to provide designers with an understanding of people's range of capabilities. Since it is not feasible to assess product interactions with a large sample, this paper assesses a range of proxy measures of design-relevant capabilities. It describes a study that was conducted to identify which measures provide the best prediction of people's abilities to use a range of products. A detailed investigation with 100 respondents aged 50-80 years was undertaken to examine how they manage typical household products. Predictor variables included self-report and performance measures across a variety of capabilities (vision, hearing, dexterity and cognitive function), component activities used in product interactions (e.g. using a remote control, touch screen) and psychological characteristics (e.g. self-efficacy, confidence with using electronic devices). Results showed, as expected, a higher prevalence of visual, hearing, dexterity, cognitive and product interaction difficulties in the 65-80 age group. Regression analyses showed that, in addition to age, performance measures of vision (acuity, contrast sensitivity) and hearing (hearing threshold) and self-report and performance measures of component activities are strong predictors of successful product interactions. These findings will guide the choice of measures to be used in a subsequent national survey of design-relevant capabilities, which will lead to the creation of a capability database. This will be converted into a tool for designers to understand the implications of their design decisions, so that they can design products in a more inclusive way.

Experimental study of load bearing cold-formed steel wall systems under fire conditions

Light Gauge Steel Framing (LSF) walls made of cold-formed and thin-walled steel lipped channel studs with plasterboard linings on both sides are commonly used in commercial, industrial and residential buildings. However, there is limited data about their structural and thermal performance under fire conditions while past research showed contradicting results about the benefits of using cavity insulation. A new composite wall panel was recently proposed to improve the fire resistance rating of LSF walls, where an insulation layer was used externally between the plasterboards on both sides of the wall frame instead of using it in the cavity. In this research 11 full scale tests were conducted on conventional load bearing steel stud walls with and without cavity insulation, and the new composite panel system to study their thermal and structural performance under standard fire conditions. These tests showed that the use of cavity insulation led to inferior fire performance of walls, and provided supporting research data. They demonstrated that the use of insulation externally in a composite panel enhanced the thermal and structural performance of LSF walls and increased their fire resistance rating. This paper presents the details of the LSF wall tests and the thermal and structural performance data and fire resistance rating of load-bearing wall assemblies lined with varying plasterboard-insulation configurations under two different load ratios. Fire test results including the time–temperature and deflection profiles are presented along with the failure times and modes.

The importance of individual characteristics in experimental economic research

This thesis advances the knowledge of behavioural economics on the importance of individual characteristics – such as gender, personality or culture – for choices relevant to labour and insurance markets. It does so using economic experiments, survey tools and physiological data, collected in economic laboratories and in the field. More specifically, the thesis includes 5 experimental economic studies investigating individual-specific characteristics (gender, age, personality, cultural background) in decisions influenced by risk attitudes and social preferences. One of these characteristics is the physiological state of decision-makers, measured by heart rate variability. The results show that individual-specific characteristics play an important role for choices affected by social preferences, a finding to a lesser degree observable for risk preferences. This finding is confirmed under revealed incentivised choices and when studying (latent) physiological responses of decision-makers.

Experimental studies of the shear behaviour and strength of lipped channel beams with web openings

Cold-formed steel members are increasingly used as primary structural elements in the building industries around the world due to the availability of thin and high strength steels and advanced cold-forming technologies. Cold-formed lipped channel beams (LCB) are commonly used as flexural members such as floor joists and bearers. However, their shear capacities are determined based on conservative design rules. Current practice in flooring systems is to include openings in the web element of floor joists or bearers so that building services can be located within them. Shear behaviour of LCBs with web openings is more complicated while their shear strengths are considerably reduced by the presence of web openings. However, limited research has been undertaken on the shear behaviour and strength of LCBs with web openings. Hence a detailed experimental study involving 40 shear tests was undertaken to investigate the shear behaviour and strength of LCBs with web openings. Simply supported test specimens of LCBs with aspect ratios of 1.0 and 1.5 were loaded at midspan until failure. This paper presents the details of this experimental study and the results of their shear capacities and behavioural characteristics. Experimental results showed that the current design rules in cold-formed steel structures design codes are very conservative for the shear design of LCBs with web openings. Improved design equations have been proposed for the shear strength of LCBs with web openings based on the experimental results from this study.

Students' perceptions of teacher biases : experimental economics in schools

We put forward a new experimental economics design with monetary incentives to estimate students’ perceptions of grading discrimination. We use this design in a large field experiment which involved 1,200 British students in grade 8 classrooms across 29 schools. In this design, students are given an endowment they can invest on a task where payoff depends on performance. The task is a written verbal test which is graded non anonymously by their teacher, in a random half of the classrooms, and graded anonymously by an external examiner in the other random half of the classrooms. We find significant evidence that students’ choices reflect perceptions of biases in teachers’ grading practices. Our results show systematic gender interaction effects: male students invest less with female teachers than with male teachers while female students invest more with male teachers than with female teachers. Interestingly, female students’ perceptions are not in line with actual discrimination: Teachers tend to give better grades to students of their own gender. Results do not suggest that ethnicity and socioeconomic status play a role. .

Tracing the influence of non-narrative film and expanded cinema sound on experimental music

This study surveys and interrogates key conceptual frameworks and artistic practises that flow through the distinct but interconnected traditions of non-narrative film and experimental music, and examines how these are articulated in my own creative sound practise.

Design of an experimental apparatus to analyse bagasse behaviour in a chute

Pressure feeder chutes are pieces of equipment used in sugar cane crushing to increase the amount of cane that can be put through a mill. The continuous pressure feeder was developed with the objective to provide a constant feed of bagasse under pressure to the mouth of the crushing mills. The pressure feeder chute is used in a sugarcane milling unit to transfer bagasse from one set of crushing rolls to a second set of crushing rolls. There have been many pressure feeder chute failures in the past. The pressure feeder chute is quite vulnerable and if the bagasse throughput is blocked at the mill rollers, the pressure build-up in the chute can be enormous, which can ultimately result in failure. The result is substantial damage to the rollers, mill and chute construction, and downtimes of up to 48 hours can be experienced. Part of the problem is that the bagasse behaviour in the pressure feeder chute is not understood well. If the pressure feeder chute behaviour was understood, then the chute geometry design could be modified in order to minimise risk of failure. There are possible avenues for changing pressure feeder chute design and operations with a view to producing more reliable pressure feeder chutes in the future. There have been previous attempts to conduct experimental work to determine the causes of pressure feeder chute failures. There are certain guidelines available, however pressure feeder chute failures continue. Pressure feeder chute behaviour still remains poorly understood. This thesis contains the work carried out between April 14th 2009 and October 10th 2012 that focuses on the design of an experimental apparatus to measure forces and visually observe bagasse behaviour in an attempt to understand bagasse behaviour in pressure feeder chutes and minimise the risk of failure.

Quantifying spatial structure in experimental observations and agent-based simulations using pair-correlation functions

We define a pair-correlation function that can be used to characterize spatiotemporal patterning in experimental images and snapshots from discrete simulations. Unlike previous pair-correlation functions, the pair-correlation functions developed here depend on the location and size of objects. The pair-correlation function can be used to indicate complete spatial randomness, aggregation or segregation over a range of length scales, and quantifies spatial structures such as the shape, size and distribution of clusters. Comparing pair-correlation data for various experimental and simulation images illustrates their potential use as a summary statistic for calibrating discrete models of various physical processes.