Data analysis methods in optometry Part 7: multiple linear regression

Multiple regression analysis is a complex statistical method with many potential uses. It has also become one of the most abused of all statistical procedures since anyone with a data base and suitable software can carry it out. An investigator should always have a clear hypothesis in mind before carrying out such a procedure and knowledge of the limitations of each aspect of the analysis. In addition, multiple regression is probably best used in an exploratory context, identifying variables that might profitably be examined by more detailed studies. Where there are many variables potentially influencing Y, they are likely to be intercorrelated and to account for relatively small amounts of the variance. Any analysis in which R squared is less than 50% should be suspect as probably not indicating the presence of significant variables. A further problem relates to sample size. It is often stated that the number of subjects or patients must be at least 5-10 times the number of variables included in the study.5 This advice should be taken only as a rough guide but it does indicate that the variables included should be selected with great care as inclusion of an obviously unimportant variable may have a significant impact on the sample size required.

The 'hard problem' and the quantum physicists. Part 2: modern times

This is the second part of a review of the work of quantum physicists on the ‘hard part’ of the problem of mind. After an introduction which sets the scene and a brief review of contemporary work on the neural correlates of consciousness (NCC) the work of four prominent modern investigators is examined: J.C. Eccles/Friedrich Beck; Henry Stapp; Stuart Hameroff/Roger Penrose; David Bohm. With the exception of David Bohm, all attempt to show where in the brain’s microstructure quantum affects could make themselves felt. It is reluctantly concluded that none have neurobiological plausibility. They are all instances, to paraphrase T.H. Huxley, of a beautiful hypothesis destroyed by ugly facts. David Bohm does not attempt to fit his new quantum physics to contemporary neurobiology but instead asks for a radical rethink of our conventional scientific paradigm. He suggests that we should look towards developing a ‘pan-experientialism’ or ‘dual-aspect monism’ where consciousness goes ‘all the way down’ and that the ‘hard problem’ is not soluble within the framework of ideas provided by ‘classical’ natural science.

Interlanguage variability in verb tense/aspect

This thesis presents a study of interlanguage variability in the use of three tense/aspect forms: the simple present, simple past, and the present perfect. The need for research in this area comes from the problems encountered in the classroom. Language performance in one task sometimes does not reflect that in another. How and why this ocurrs is what this thesis aims to discover. A preliminary study explores the viability of using the Labovian variable model to elicit and explain variability. Difficulties highlight problems which help refine the methodology used in the main study. A review of past research point the direction in which this study should go. Armed with a sample of 17 Chinese Singaporean university students, whose first language is Chinese or a dialect of Chinese, the investigation began with the elicitation of variability to be found in four tasks. Using the attention-to-speech framework, these four tasks are designed to reflect varying degrees of required attention to language form. The results show that there is variability in the use of tense/aspect in all the tasks. However, the framework on which the tasks are based cannot explain the variability pattern. Further analyses of contextual factors, primarily pragmatic ones, point to a complex interplay of factors affecting the variability found in the results.

The pathogenesis of Alzheimer's disease: a reevaluation of the "amyloid cascade hypothesis"

The most influential theory to explain the pathogenesis of Alzheimer's disease (AD) has been the "Amyloid Cascade Hypothesis" (ACH) first formulated in 1992. The ACH proposes that the deposition of ß-amyloid (Aß) is the initial pathological event in AD leading to the formation of senile plaques (SPs) and then to neurofibrillary tangles (NFTs) death of neurons, and ultimately dementia. This paper examines two questions regarding the ACH: (1) is there a relationship between the pathogenesis of SPs and NFTs, and (2) what is the relationship of these lesions to disease pathogenesis? These questions are examined in relation to studies of the morphology and molecular determinants of SPs and NFTs, the effects of gene mutation, degeneration induced by head injury, the effects of experimentally induced brain lesions, transgenic studies, and the degeneration of anatomical pathways. It was concluded that SPs and NFTs develop independently and may be the products rather than the causes of neurodegeneration in AD. A modification to the ACH is proposed which may better explain the pathogenesis of AD, especially of late-onset cases of the disease.

Self-assembly of trehalose molecules on a lysozyme surface: the broken glass hypothesis

To help understand how sugar interactions with proteins stabilise biomolecular structures, we compare the three main hypotheses for the phenomenon with the results of long molecular dynamics simulations on lysozyme in aqueous trehalose solution (0.75 M). We show that the water replacement and water entrapment hypotheses need not be mutually exclusive, because the trehalose molecules assemble in distinctive clusters on the surface of the protein. The flexibility of the protein backbone is reduced under the sugar patches supporting earlier findings that link reduced flexibility of the protein with its higher stability. The results explain the apparent contradiction between different experimental and theoretical results for trehalose effects on proteins.

Fabrication of high aspect ratio microfluidic devices using direct FS ablation

We present a single stage direct fs ablation results which show that it is possible to make high quality and high aspect ratio devices in a single stage process using a CAD optimised approach.

Further studies on the patterns of senile plaques in senile dementia of the Alzheimer type (SDAT) with a hypothesis on the colonization of the cortex

The pattern of senile plaques was investigated in various brain regions of six SDAT brains. In 91 pattern analyses, the regularly spaced clump was the most common pattern found in 64.8% of analyses. Clumping due to large aggregations of uncored plaques in sulci was also common. Regularly spaced clumps were equally common in the hippocampus and neocortex. The pattern of plaques varied in different tissue sections from the same brain region. Cored and uncored plaques presented a similar range of patterns but their pattern varied when they were both present in the same tissue section. Both clump diameter and the intensity of clumping were positively correlated with cored but unrelated to uncored plaque density. Plaques may develop in regular clumps on subcortical afferents and during development of the disease the clumps may spread laterally and ultimately coalesce.

The spatial patterns of plaques and tangles in Alzheimer's disease do not support the 'cascade hypothesis'

In Alzheimer's disease (AD), the 'Cascade hypothesis' proposes that the formation of paired helical filaments (PHF) may be casually linked to the deposition of beta/A4 protein. Hence, there should be a close spatial relationship between senile plaques and cellular neurofibrillary tangles in a local region of the brain. In tissue from 6 AD patients, plaques and tangles occurred in clusters and individual clusters were often regularly spaced along the cortical strip. However, the clusters of plaques and tangles were in phase in only 4/32 cortical tissues examined. Hence, the data were not consistent with the 'Cascade hypothesis' that beta/A4 and PHF are directly linked in AD.

Effect of aspect ratio on thermal convection in open and closed systems

Internally heated fluids are found across the nuclear fuel cycle. In certain situations the motion of the fluid is driven by the decay heat (i.e. corium melt pools in severe accidents, the shutdown of liquid metal reactors, molten salt and the passive control of light water reactors) as well as normal operation (i.e. intermediate waste storage and generation IV reactor designs). This can in the long-term affect reactor vessel integrity or lead to localized hot spots and accumulation of solid wastes that may prompt local increases in activity. Two approaches to the modeling of internally heated convection are presented here. These are based on numerical analysis using codes developed in-house and simulations using widely available computational fluid dynamics solvers. Open and closed fluid layers at around the transition between conduction and convection of various aspect ratios are considered. We determine optimum domain aspect ratio (1:7:7 up to 1:24:24 for open systems and 5:5:1, 1:10:10 and 1:20:20 for closed systems), mesh resolutions and turbulence models required to accurately and efficiently capture the convection structures that evolve when perturbing the conductive state of the fluid layer. Note that the open and closed fluid layers we study here are bounded by a conducting surface over an insulating surface. Conclusions will be drawn on the influence of the periodic boundary conditions on the flow patterns observed. We have also examined the stability of the nonlinear solutions that we found with the aim of identifying the bifurcation sequence of these solutions en route to turbulence.

An aspect-oriented and model-driven approach for managing dynamic variability

Constructing and executing distributed systems that can adapt to their operating context in order to sustain provided services and the service qualities are complex tasks. Managing adaptation of multiple, interacting services is particularly difficult since these services tend to be distributed across the system, interdependent and sometimes tangled with other services. Furthermore, the exponential growth of the number of potential system configurations derived from the variabilities of each service need to be handled. Current practices of writing low-level reconfiguration scripts as part of the system code to handle run time adaptation are both error prone and time consuming and make adaptive systems difficult to validate and evolve. In this paper, we propose to combine model driven and aspect oriented techniques to better cope with the complexities of adaptive systems construction and execution, and to handle the problem of exponential growth of the number of possible configurations. Combining these techniques allows us to use high level domain abstractions, simplify the representation of variants and limit the problem pertaining to the combinatorial explosion of possible configurations. In our approach we also use models at runtime to generate the adaptation logic by comparing the current configuration of the system to a composed model representing the configuration we want to reach. © 2008 Springer-Verlag Berlin Heidelberg.

Fabrication of high aspect ratio microfluidic devices using direct FS ablation

We present a single stage direct fs ablation results which show that it is possible to make high quality and high aspect ratio devices in a single stage process using a CAD optimised approach.

Bifurcation study for a vertical channel with constant flux and large aspect ratio

Using suitable coupled Navier-Stokes Equations for an incompressible Newtonian fluid we investigate the linear and non-linear steady state solutions for both a homogeneously and a laterally heated fluid with finite Prandtl Number (Pr=7) in the vertical orientation of the channel. Both models are studied within the Large Aspect Ratio narrow-gap and under constant flux conditions with the channel closed. We use direct numerics to identify the linear stability criterion in parametric terms as a function of Grashof Number (Gr) and streamwise infinitesimal perturbation wavenumber (making use of the generalised Squire’s Theorem). We find higher harmonic solutions at lower wavenumbers with a resonance of 1:3exist, for both of the heating models considered. We proceed to identify 2D secondary steady state solutions, which bifurcate from the laminar state. Our studies show that 2D solutions are found not to exist in certain regions of the pure manifold, where we find that 1:3 resonant mode 2D solutions exist, for low wavenumber perturbations. For the homogeneously heated fluid, we notice a jump phenomenon existing between the pure and resonant mode secondary solutions for very specific wavenumbers .We attempt to verify whether mixed mode solutions are present for this model by considering the laterally heated model with the same geometry. We find mixed mode solutions for the laterally heated model showing that a bridge exists between the pure and 1:3 resonant mode 2D solutions, of which some are stationary and some travelling. Further, we show that for the homogeneously heated fluid that the 2D solutions bifurcate in hopf bifurcations and there exists a manifold where the 2D solutions are stable to Eckhaus criterion, within this manifold we proceed to identify 3D tertiary solutions and find that the stability for said 3D bifurcations is not phase locked to the 2D state. For the homogeneously heated model we identify a closed loop within the neutral stability curve for higher perturbation wavenumubers and analyse the nature of the multiple 2D bifurcations around this loop for identical wavenumber and find that a temperature inversion occurs within this loop. We conclude that for a homogeneously heated fluid it is possible to have abrup ttransitions between the pure and resonant 2D solutions, and that for the laterally heated model there exist a transient bifurcation via mixed mode solutions.