Tonometry:a study in biomechanical modelling. Appraisal and utility of measurable biomechanical markers.

Goldmann Applanation Tonometry (GAT) is the recognised ‘Gold Standard’ tonometer.However this status is refuted by eminent authors. These contradictory views have driventhe initial goal to assess, from first principles, the evolution of GAT and to experimentallyevaluate its utility and corrections. Subsequently, an important caveat became theevaluation of Corneal Hysteresis and Corneal Resistance Factor.Chapter 1. Biomechanical building blocks are defined and constitutive principlesincorporated into continuum modelling. The Imbert-Fick construct is re-interpreted asimple biomechanical model. GAT corrections are also appraised within a continuumframework; CCT, geometry and stiffness. These principles enable evaluation ofalternative tonometer theory and the evolving biomechanical markers, CornealHysteresis (ORA-CH) and Corneal Resistance Factor (ORA-CRF).Chapter 2 appraises corneal biomechanical markers, CCT, curvature, ORA-CH andORA-CRF in 91 normal eyes and the impact these have on three tonometers: GAT,Tonopen and Ocular Response Analyser (ORA). Tonopen was the sole tonometer notaffected by biomechanics. CCT was confirmed the sole measurable parameter affectingGAT. ORA did not demonstrate improved utility. ORA-CH and ORA-CRF do not appearrobust biomechanical measures.Chapter 3 assessed agreement between GAT, the ORA measures and Tonopen.Tonopen is found to measure highest and raises the question should a development goalemphasise GAT agreement or improvement?Chapter 4 assessed repeatability of the three tonometers and biomechanical measureskeratometry, pachymetry, ORA-CH and ORA-CRF on 35 eyes. Coefficients ofRepeatability (CoR) of all tonometers are wide. Effects assessed in Chapter 5 may bemasked by general noise. ORA does not appear to enhance utility over GAT.Isolation of corneal shape change via Orthokeratology (Chapter 5) demonstrate ORACHand ORA-CRF reflect, predominantly, a response to corneal flattening. It is proposedthey do not significantly reflect corneal biomechanics.After reviewing models for tear forces (Chapter 6), a refined mathematical model ispresented. Tear bridge attraction is minimal and cannot explain under-estimation of IOPby GAT in thin corneas. CCT corrections and the Imbert-Fick rules are incompatible.Chapter 7 summarises findings. The supremacy of GAT is likely to remain for some time,reflecting the sheer magnitude of overturning 60 years of convention, historicalprecedent, expert opinion as well as the logistical and educational difficulties ofredefining standards and statistical norms

Perturbative Inaccessibility of Conformal Fixed Points in Nonsupersymmetric Quiver Theories

The possibility that non-supersymmetric quiver theories may have a renormalization-group fixed point at which there is conformal invariance requires non-perturbative information.The possibility that non-supersymmetric quiver theories may have a renormalization-group fixed point at which there is conformal invariance requires non-perturbative information

Bipolar Disorder and the TCI: Higher Self-Transcendence in Bipolar Disorder Compared to Major Depression

Personality traits are potential endophenotypes for genetic studies of psychiatric disorders. One personality theory which demonstrates strong heritability is Cloninger's psychobiological model measured using the temperament and character inventory (TCI). 277 individuals who completed the TCI questionnaire as part of the South Island Bipolar Study were also interviewed to assess for lifetime psychiatric diagnoses. Four groups were compared, bipolar disorder (BP), type 1 and 2, MDD (major depressive disorder), and nonaffected relatives of a proband with BP. With correction for mood state, total harm avoidance (HA) was higher than unaffected in both MDD and BP groups, but the mood disorder groups did not differ from each other. However, BP1 individuals had higher self-transcendence (ST) than those with MDD and unaffected relatives. HA may reflect a trait marker of mood disorders whereas high ST may be specific to BP. As ST is heritable, genes that affect ST may be of relevance for vulnerability to BP

Signatures for a Cosmic Flux of Magnetic Monopoles

Any early universe phase transition occurring after inflation has the potential to populate the universe with relic magnetic monopoles. Observations of galactic magnetic fields, as well as observations matched with models for extragalactic magnetic fields, lead to the conclusion that monopoles of mass \lsim 10^{15} GeV are accelerated in these fields to relativistic velocities. We explore the possible signatures of a cosmic flux of relativistic monopoles impinging on the earth. The electromagnetically-induced signatures of monopoles are reliable. The hadronically-induced signatures are highly model-dependent. Among our findings are (i) the electromagnetic energy losses of monopoles continuously initiate a protracted shower of small intensity; (ii) monopoles may traverse the earth's diameter, making them a probe of the earth's interior structure; (iii) in addition to the direct monopole Cherenkov signal presently employed, a very attractive search strategy for monopoles is detection of their radio-Cherenkov signal produced by the coherent charge-excess in the $e^+-e^-$ shower - in fact, Cherenkov-detectors have the potential to discover a monopole flux (or limit it) several orders of magnitude below the theoretical Parker limit of $10^{-15}/\rm{cm}^2$/s/sr; (iv) it is conceivable (but not compelling) that bound states of colored monopoles may be the primary particles initiating the air showers observed above the GZK cutoff.Comment: 33 pages, 5 figures, revtex, to appear in Astro. Part. Phy

A Model of Quark and Lepton Masses I: The Neutrino Sector

If neutrinos have masses, why are they so tiny? Are these masses of the Dirac type or of the Majorana type? We are already familiar with the mechanism of how to obtain a tiny Majorana neutrino mass by the famous see-saw mechanism. The question is: Can one build a model in which a tiny Dirac neutrino mass arises in a more or less "natural" way? What would be the phenomenological consequences of such a scenario, other than just merely reproducing the neutrino mass patterns for the oscillation data? In this article, a systematic and detailed analysis of a model is presented, with, as key components, the introduction of a family symmetry as well as a new SU(2) symmetry for the right-handed neutrinos. In particular, in addition to the calculations of light neutrino Dirac masses, interesting phenomenological implications of the model will be presented.Comment: 25 (single-spaced) pages, 11 figures, corrected some typos in Table I, added acknowledgement

Development and assessment of a bone scanning device to enhance restraint performance

The objective of the BOSCOS (BOne Scanning for Occupant Safety) project was the development of a system that can make an assessment of the bone characteristics of each vehicle occupant in order to estimate their skeletal strengths. The seatbelt and airbag characteristics can then be adjusted to deliver optimum levels of protection specifically for each occupant. A system introduced into every vehicle has the capacity to save lives and reduce injury levels across the whole spectrum of vehicle occupants. This paper describes the contributions from academic and industrial partners to this UK Department for Transport funded project.Commercial pressure focuses restraint design on meeting legal requirements for vehicle approval, but legal requirements use dummies which do not represent the range of car occupant shapes, sizes, and driving positions. A person with lower skeletal characteristics may not be able to withstand the current fixed levels of restraint without sustaining injuries. Conversely, a person with greater skeletal characteristics may be capable of withstanding greater levels of restraint.Possible technologies that are available have been assessed for their suitability for an in-vehicle monitoring system. Accident studies have been conducted to create a baseline of statistics in terms of casualties and their injuries. Initial bone scanning studies have utilised different types of equipment and a new prototype scanner has been developed for use in a vehicle environment using ultrasound technology.Computer based occupant mathematical modelling has been used to establish the potential gains from a working system and also the requirements needed of the restraint systems toachieve these gains. In addition, bone scanning has been conducted, to determine a method to read across from scan values to skeletal condition to provide data for the optimisation of the restraint system

Ultra High Energy Cosmic Rays from Sequestered X Bursts

Assuming that there is no GZK (Greisen-Zatsepin-Kuzmin) cut-off and that super-GZK cosmic rays correlate with AGN (Active Galactic Nuclei) at cosmological distances, it is speculated that a relic superheavy particle (X) has its lifetime enhanced by sequestration in an extra dimension. This sequestration is assumed to be partially liberated by proximity of merging supermassive black holes in an AGN, temporarily but drastically reducing the lifetime, thus stimulating an X burst. Based on sequestration of the decay products of X, a speculative explanation of the observed $\gamma/N$ ratio is proposed.Comment: 12 pages LaTe

An association study of DRD2 and COMT polymorphisms with novelty seeking and harm avoidance scores, in two independent samples of depressed patients

BACKGROUND: It was recently reported that an interaction of the dopamine D2 receptor (DRD2) and catechol-O-methyltransferase (COMT) influences the behavioural approach system – as measured using Carver and White's Behavioural Inhibition and Behavioural Approach System (BIS/BAS) scales – in a sample of healthy German subjects. The Temperament and Character Inventory (TCI), in particular the novelty seeking (NS) and harm avoidance (HA) scales, correlates moderately with the BIS/BAS measure. This study aimed to examine support for an association of DRD2 and COMT with behavioural activation, using the TCI within two independent samples of depressed outpatients (for both samples n = 146). METHODS: Two clinical samples of depressed patients were ascertained to assess the efficacy of two different pharmacotherapy and psychotherapy treatments. Analysis of variance (ANOVA) was used to analyse NS and HA scale and subscale scores with respect to gene loci within each clinical sample. Analysis of covariance were undertaken to examine the association of age and gender with NS and HA scores. An association of age group or gender with gene loci were explored using chi-squared tests, in each sample. RESULTS: No significant effect of DRD2 or COMT, either independently or as an interaction, on NS or HA scores was observed, within either sample. Whilst age was significantly negatively associated with NS scores, including age in the two- and three-way interactions did not affect the significance of the association of personality with gene loci. CONCLUSION: This study suggests that the COMT-DRD2 Equilibrium Model of Positive Emotionality recently proposed by Reuter and his colleagues is not applicable amongst currently depressed individuals, whose behavioural approach and inhibition tendencies have been assessed using the TCI

The utility of presentation and 4-hour high sensitivity troponin I to rule-out acute myocardial infarction in the emergency department

Objectives: International guidance recommends that early serial sampling of high sensitivity troponin be used to accurately identify acute myocardial infarction (AMI) in chest pain patients. The background evidence for this approach is limited. We evaluated whether on presentation and 4-hour high-sensitivity troponin I (hs-cTnI) could be used to accurately rule-out AMI. Design and methods: hs-cTnI was measured on presentation and at 4-hours in adult patients attending an emergency department with possible acute coronary syndrome. We determined the sensitivity for AMI for at least one hs-cTnI above the 99th percentile for a healthy population or alone or in combination with new ischemic ECG changes. Both overall and sex-specific 99th percentiles were assessed. Patients with negative tests were designated low-risk. Results: 63 (17.1%) of 368 patients had AMI. The median (interquartile range) time from symptom onset to first blood sampling was 4.8. h (2.8-8.6). The sensitivity of the presentation and 4. h hs-cTnI using the overall 99th percentile was 92.1% (95% CI 82.4% to 97.4%) and negative predictive value 95.4% (92.3% to 97.4%) with 78.3% low-risk. Applying the sex-specific 99th percentile did not change the sensitivity. The addition of ECG did not change the sensitivity. Conclusion: Hs-cTnI >. 99th percentile thresholds measured on presentation and at 4-hours was not a safe strategy to rule-out AMI in this clinical setting irrespective of whether sex-specific 99th percentiles were used, or whether hs-cTnI was combined with ECG results