Development of Contact Lenses from a Biomaterial Point of View – Materials, Manufacture, and Clinical Application

Rigid lenses, which were originally made from glass (between 1888 and 1940) and later from polymethyl methacrylate or silicone acrylate materials, are uncomfortable to wear and are now seldom fitted to new patients. Contact lenses became a popular mode of ophthalmic refractive error correction following the discovery of the first hydrogel material – hydroxyethyl methacrylate – by Czech chemist Otto Wichterle in 1960. To satisfy the requirements for ocular biocompatibility, contact lenses must be transparent and optically stable (for clear vision), have a low elastic modulus (for good comfort), have a hydrophilic surface (for good wettability), and be permeable to certain metabolites, especially oxygen, to allow for normal corneal metabolism and respiration during lens wear. A major breakthrough in respect of the last of these requirements was the development of silicone hydrogel soft lenses in 1999 and techniques for making the surface hydrophilic. The vast majority of contact lenses distributed worldwide are mass-produced using cast molding, although spin casting is also used. These advanced mass-production techniques have facilitated the frequent disposal of contact lenses, leading to improvements in ocular health and fewer complications. More than one-third of all soft contact lenses sold today are designed to be discarded daily (i.e., ‘daily disposable’ lenses).

Efficient fuzzy matching and intersection on private datasets

At Eurocrypt’04, Freedman, Nissim and Pinkas introduced a fuzzy private matching problem. The problem is defined as follows. Given two parties, each of them having a set of vectors where each vector has T integer components, the fuzzy private matching is to securely test if each vector of one set matches any vector of another set for at least t components where t < T. In the conclusion of their paper, they asked whether it was possible to design a fuzzy private matching protocol without incurring a communication complexity with the factor (T t ) . We answer their question in the affirmative by presenting a protocol based on homomorphic encryption, combined with the novel notion of a share-hiding error-correcting secret sharing scheme, which we show how to implement with efficient decoding using interleaved Reed-Solomon codes. This scheme may be of independent interest. Our protocol is provably secure against passive adversaries, and has better efficiency than previous protocols for certain parameter values.

Patient-specific computational biomechanics for simulating adolescent scoliosis surgery : predicted vs clinical correction for a preliminary series of six patients

Scoliosis is a spinal deformity that requires surgical correction in progressive cases. In order to optimize surgical outcomes, patient-specific finite element models are being developed by our group. In this paper, a single rod anterior correction procedure is simulated for a group of six scoliosis patients. For each patient, personalised model geometry was derived from low-dose CT scans, and clinically measured intra-operative corrective forces were applied. However, tissue material properties were not patient-specific, being derived from existing literature. Clinically, the patient group had a mean initial Cobb angle of 47.3 degrees, which was corrected to 17.5 degrees after surgery. The mean simulated post-operative Cobb angle for the group was 18.1 degrees. Although this represents good agreement between clinical and simulated corrections, the discrepancy between clinical and simulated Cobb angle for individual patients varied between -10.3 and +8.6 degrees, with only three of the six patients matching the clinical result to within accepted Cobb measurement error of +-5 degrees. The results of this study suggest that spinal tissue material properties play an important role in governing the correction obtained during surgery, and that patient-specific modelling approaches must address the question of how to prescribe patient-specific soft tissue properties for spine surgery simulation.

Design of a preliminary error impact analysis model for spatial safety assessment of earthmoving operations

Regardless of technology benefits, safety planners still face difficulties explaining errors related to the use of different technologies and evaluating how the errors impact the performance of safety decision making. This paper presents a preliminary error impact analysis testbed to model object identification and tracking errors caused by image-based devices and algorithms and to analyze the impact of the errors for spatial safety assessment of earthmoving and surface mining activities. More specifically, this research designed a testbed to model workspaces for earthmoving operations, to simulate safety-related violations, and to apply different object identification and tracking errors on the data collected and processed for spatial safety assessment. Three different cases were analyzed based on actual earthmoving operations conducted at a limestone quarry. Using the testbed, the impacts of the errors were investigated for the safety planning purpose.

Model selection and error estimation

We study model selection strategies based on penalized empirical loss minimization. We point out a tight relationship between error estimation and data-based complexity penalization: any good error estimate may be converted into a data-based penalty function and the performance of the estimate is governed by the quality of the error estimate. We consider several penalty functions, involving error estimates on independent test data, empirical VC dimension, empirical VC entropy, and margin-based quantities. We also consider the maximal difference between the error on the first half of the training data and the second half, and the expected maximal discrepancy, a closely related capacity estimate that can be calculated by Monte Carlo integration. Maximal discrepancy penalty functions are appealing for pattern classification problems, since their computation is equivalent to empirical risk minimization over the training data with some labels flipped.

Fast rates for estimation error and oracle inequalities for model section

We consider complexity penalization methods for model selection. These methods aim to choose a model to optimally trade off estimation and approximation errors by minimizing the sum of an empirical risk term and a complexity penalty. It is well known that if we use a bound on the maximal deviation between empirical and true risks as a complexity penalty, then the risk of our choice is no more than the approximation error plus twice the complexity penalty. There are many cases, however, where complexity penalties like this give loose upper bounds on the estimation error. In particular, if we choose a function from a suitably simple convex function class with a strictly convex loss function, then the estimation error (the difference between the risk of the empirical risk minimizer and the minimal risk in the class) approaches zero at a faster rate than the maximal deviation between empirical and true risks. In this paper, we address the question of whether it is possible to design a complexity penalized model selection method for these situations. We show that, provided the sequence of models is ordered by inclusion, in these cases we can use tight upper bounds on estimation error as a complexity penalty. Surprisingly, this is the case even in situations when the difference between the empirical risk and true risk (and indeed the error of any estimate of the approximation error) decreases much more slowly than the complexity penalty. We give an oracle inequality showing that the resulting model selection method chooses a function with risk no more than the approximation error plus a constant times the complexity penalty.

The Bayesian conditional independence model for measurement error: applications in ecology

The measurement error model is a well established statistical method for regression problems in medical sciences, although rarely used in ecological studies. While the situations in which it is appropriate may be less common in ecology, there are instances in which there may be benefits in its use for prediction and estimation of parameters of interest. We have chosen to explore this topic using a conditional independence model in a Bayesian framework using a Gibbs sampler, as this gives a great deal of flexibility, allowing us to analyse a number of different models without losing generality. Using simulations and two examples, we show how the conditional independence model can be used in ecology, and when it is appropriate.

Correction of step artefact associated with MRI scanning of long bones

3D models of long bones are being utilised for a number of fields including orthopaedic implant design. Accurate reconstruction of 3D models is of utmost importance to design accurate implants to allow achieving a good alignment between two bone fragments. Thus for this purpose, CT scanners are employed to acquire accurate bone data exposing an individual to a high amount of ionising radiation. Magnetic resonance imaging (MRI) has been shown to be a potential alternative to computed tomography (CT) for scanning of volunteers for 3D reconstruction of long bones, essentially avoiding the high radiation dose from CT. In MRI imaging of long bones, the artefacts due to random movements of the skeletal system create challenges for researchers as they generate inaccuracies in the 3D models generated by using data sets containing such artefacts. One of the defects that have been observed during an initial study is the lateral shift artefact occurring in the reconstructed 3D models. This artefact is believed to result from volunteers moving the leg during two successive scanning stages (the lower limb has to be scanned in at least five stages due to the limited scanning length of the scanner). As this artefact creates inaccuracies in the implants designed using these models, it needs to be corrected before the application of 3D models to implant design. Therefore, this study aimed to correct the lateral shift artefact using 3D modelling techniques. The femora of five ovine hind limbs were scanned with a 3T MRI scanner using a 3D vibe based protocol. The scanning was conducted in two halves, while maintaining a good overlap between them. A lateral shift was generated by moving the limb several millimetres between two scanning stages. The 3D models were reconstructed using a multi threshold segmentation method. The correction of the artefact was achieved by aligning the two halves using the robust iterative closest point (ICP) algorithm, with the help of the overlapping region between the two. The models with the corrected artefact were compared with the reference model generated by CT scanning of the same sample. The results indicate that the correction of the artefact was achieved with an average deviation of 0.32 ± 0.02 mm between the corrected model and the reference model. In comparison, the model obtained from a single MRI scan generated an average error of 0.25 ± 0.02 mm when compared with the reference model. An average deviation of 0.34 ± 0.04 mm was seen when the models generated after the table was moved were compared to the reference models; thus, the movement of the table is also a contributing factor to the motion artefacts.

Evaluation of a patient-specific finite-element model to simulate conservative treatment in adolescent idiopathic scoliosis

Study design Retrospective validation study. Objectives To propose a method to evaluate, from a clinical standpoint, the ability of a finite-element model (FEM) of the trunk to simulate orthotic correction of spinal deformity and to apply it to validate a previously described FEM. Summary of background data Several FEMs of the scoliotic spine have been described in the literature. These models can prove useful in understanding the mechanisms of scoliosis progression and in optimizing its treatment, but their validation has often been lacking or incomplete. Methods Three-dimensional (3D) geometries of 10 patients before and during conservative treatment were reconstructed from biplanar radiographs. The effect of bracing was simulated by modeling displacements induced by the brace pads. Simulated clinical indices (Cobb angle, T1–T12 and T4–T12 kyphosis, L1–L5 lordosis, apical vertebral rotation, torsion, rib hump) and vertebral orientations and positions were compared to those measured in the patients' 3D geometries. Results Errors in clinical indices were of the same order of magnitude as the uncertainties due to 3D reconstruction; for instance, Cobb angle was simulated with a root mean square error of 5.7°, and rib hump error was 5.6°. Vertebral orientation was simulated with a root mean square error of 4.8° and vertebral position with an error of 2.5 mm. Conclusions The methodology proposed here allowed in-depth evaluation of subject-specific simulations, confirming that FEMs of the trunk have the potential to accurately simulate brace action. These promising results provide a basis for ongoing 3D model development, toward the design of more efficient orthoses.

Robust estimating functions and bias correction for longitudinal data analysis

Robust methods are useful in making reliable statistical inferences when there are small deviations from the model assumptions. The widely used method of the generalized estimating equations can be "robustified" by replacing the standardized residuals with the M-residuals. If the Pearson residuals are assumed to be unbiased from zero, parameter estimators from the robust approach are asymptotically biased when error distributions are not symmetric. We propose a distribution-free method for correcting this bias. Our extensive numerical studies show that the proposed method can reduce the bias substantially. Examples are given for illustration.

Competence in Intelligence Testing : A Training Model for Postgraduate Psychology Students

The assessment of intellectual ability is a core competency in psychology. The results of intelligence tests have many potential implications and are used frequently as the basis for decisions about educational placements, eligibility for various services, and admission to specific groups. Given the importance of intelligence test scores, accurate test administration and scoring are essential; yet there is evidence of unacceptably high rates of examiner error. This paper discusses competency and postgraduate training in intelligence testing and presents a training model for postgraduate psychology students. The model aims to achieve high levels of competency in intelligence testing through a structured method of training, practice and feedback that incorporates peer support, self-reflection and multiple methods for evaluating competency.

Development of a computer simulation tool for application in adolescent spinal deformity surgery

Scoliosis is a three-dimensional spinal deformity which requires surgical correction in progressive cases. In order to optimize correction and avoid complications following scoliosis surgery, patient-specific finite element models (FEM) are being developed and validated by our group. In this paper, the modeling methodology is described and two clinically relevant load cases are simulated for a single patient. Firstly, a pre-operative patient flexibility assessment, the fulcrum bending radiograph, is simulated to assess the model's ability to represent spine flexibility. Secondly, intra-operative forces during single rod anterior correction are simulated. Clinically, the patient had an initial Cobb angle of 44 degrees, which reduced to 26 degrees during fulcrum bending. Surgically, the coronal deformity corrected to 14 degrees. The simulated initial Cobb angle was 40 degrees, which reduced to 23 degrees following the fulcrum bending load case. The simulated surgical procedure corrected the coronal deformity to 14 degrees. The computed results for the patient-specific FEM are within the accepted clinical Cobb measuring error of 5 degrees, suggested that this modeling methodology is capable of capturing the biomechanical behaviour of a scoliotic human spine during anterior corrective surgery.

Anterior vertebral stapling for the fusionless correction of scoliosis

Fusionless scoliosis surgery is an emerging treatment for idiopathic scoliosis as it offers theoretical advantages over current forms of treatment. Currently the treatment options for idiopathic scoliosis are observation, bracing and fusion. While brace treatment is non-invasive, and preserves the growth, motion, and function of the spine, it does not correct deformity and is only modestly successful in preventing curve progression. In adolescents who fail brace treatment, surgical treatment with an instrumented spinal fusion usually results in better deformity correction but is associated with substantially greater risk. Furthermore in younger patients requiring surgical treatment, fusion procedures are known to adversely effect the future growth of the chest and spine. Fusionless treatments have been developed to allow effective surgical treatment of patients with idiopathic scoliosis who are too young for fusion procedures. Anterior vertebral stapling is one such fusionless treatment which aims to modulate the growth of vertebra to allow correction of scoliosis whilst maintaining normal spinal motion The Mater Misericordiae Hospital in Brisbane has begun to use anterior vertebral stapling to treat patients with idiopathic scoliosis who are too young for fusion procedures. Currently the only staple approved for clinical use is manufactured by Medtronic Sofamor Danek (Memphis, TN). This thesis explains the biomechanical and anatomical changes that occur following anterior vertebral staple insertion using in vitro experiments performed on an immature bovine model. Currently there is a paucity of published information about anterior vertebral stapling so it is hoped that this project will provide information that will aid in our understanding of the clinical effects of staple insertion. The aims of this experimental study were threefold. The first phase was designed to determine the changes in the bending stiffness of the spine following staple insertion. The second phase was designed to measure the forces experienced by the staple during spinal movements. The third and final phase of testing was designed to describe the structural changes that occur to a vertebra as a consequence of staple insertion. The first phase of testing utilised a displacement controlled testing robot to compare the change in stiffness of a single spinal motion segment following staple insertion for the three basic spinal motions of flexion-extension, lateral bending, and axial rotation. For the second phase of testing strain gauges were attached to staples and used to measure staple forces during spinal movement. In the third and final phase the staples were removed and a testing specimen underwent micro-computed tomography (CT) scanning to describe the anatomical changes that occur following staple insertion. The displacement controlled testing showed that there was a significant decrease in bending stiffness in flexion, extension, lateral bending away from the staple, and axial rotation away from the staple following staple insertion. The strain gauge measurements showed that the greatest staple forces occurred in flexion and the least in extension. In addition, a reduction in the baseline staple compressive force was seen with successive loading cycles. Micro-CT scanning demonstrated that significant damage to the vertebral body and endplate occurred as a consequence of staple insertion. The clinical implications of this study are significant. Based on the findings of this project it is likely that the clinical effect of the anterior vertebral staple evaluated in this project is a consequence of growth plate damage (also called hemiepiphysiodesis) causing a partial growth arrest of the vertebra rather than simply compression of the growth plate. The surgical creation of a unilateral growth arrest is a well established treatment used in the management of congenital scoliosis but has not previously been considered for use in idiopathic scoliosis.

The applicability of biased estimation in model and model order selection

Biased estimation has the advantage of reducing the mean squared error (MSE) of an estimator. The question of interest is how biased estimation affects model selection. In this paper, we introduce biased estimation to a range of model selection criteria. Specifically, we analyze the performance of the minimum description length (MDL) criterion based on biased and unbiased estimation and compare it against modern model selection criteria such as Kay's conditional model order estimator (CME), the bootstrap and the more recently proposed hook-and-loop resampling based model selection. The advantages and limitations of the considered techniques are discussed. The results indicate that, in some cases, biased estimators can slightly improve the selection of the correct model. We also give an example for which the CME with an unbiased estimator fails, but could regain its power when a biased estimator is used.

Model round-trip engineering

In the quest for shorter time-to-market, higher quality and reduced cost, model-driven software development has emerged as a promising approach to software engineering. The central idea is to promote models to first-class citizens in the development process. Starting from a set of very abstract models in the early stage of the development, they are refined into more concrete models and finally, as a last step, into code. As early phases of development focus on different concepts compared to later stages, various modelling languages are employed to most accurately capture the concepts and relations under discussion. In light of this refinement process, translating between modelling languages becomes a time-consuming and error-prone necessity. This is remedied by model transformations providing support for reusing and automating recurring translation efforts. These transformations typically can only be used to translate a source model into a target model, but not vice versa. This poses a problem if the target model is subject to change. In this case the models get out of sync and therefore do not constitute a coherent description of the software system anymore, leading to erroneous results in later stages. This is a serious threat to the promised benefits of quality, cost-saving, and time-to-market. Therefore, providing a means to restore synchronisation after changes to models is crucial if the model-driven vision is to be realised. This process of reflecting changes made to a target model back to the source model is commonly known as Round-Trip Engineering (RTE). While there are a number of approaches to this problem, they impose restrictions on the nature of the model transformation. Typically, in order for a transformation to be reversed, for every change to the target model there must be exactly one change to the source model. While this makes synchronisation relatively “easy”, it is ill-suited for many practically relevant transformations as they do not have this one-to-one character. To overcome these issues and to provide a more general approach to RTE, this thesis puts forward an approach in two stages. First, a formal understanding of model synchronisation on the basis of non-injective transformations (where a number of different source models can correspond to the same target model) is established. Second, detailed techniques are devised that allow the implementation of this understanding of synchronisation. A formal underpinning for these techniques is drawn from abductive logic reasoning, which allows the inference of explanations from an observation in the context of a background theory. As non-injective transformations are the subject of this research, there might be a number of changes to the source model that all equally reflect a certain target model change. To help guide the procedure in finding “good” source changes, model metrics and heuristics are investigated. Combining abductive reasoning with best-first search and a “suitable” heuristic enables efficient computation of a number of “good” source changes. With this procedure Round-Trip Engineering of non-injective transformations can be supported.