Cardiac magnetic resonance imaging assessment of aortic stenosis to improve clinical care

Background Aortic stenosis is the commonest valve disease requiring intervention in the developed world. Current guideline-based management strategies are based on historical observational data or expert opinion and may leave many patients with irreversible myocardial damage and adverse outcomes following valve intervention. The aims of this thesis are to investigate novel cardiac magnetic resonance techniques and how they can be applied to improve our decision making around the timing of valve intervention. Methods and Results Cardiac magnetic resonance imaging can detect two forms of myocardial fibrosis non-invasively; diffuse fibrosis using T1 mapping and replacement fibrosis with the late gadolinium enhancement technique. I devised a novel measure of diffuse fibrosis, the indexed extracellular volume (iECV) and showed that these techniques can be used to divide patients into three categories according to the type and amount of fibrosis present: no fibrosis, diffuse fibrosis and replacement fibrosis. Moreover, I demonstrated that there was evidence of increasing left ventricular decompensation across these three groups. How fibrosis and left ventricular hypertrophy change over time has not been well studied in patients with aortic stenosis. Using serial imaging scans, I showed that hypertrophy and diffuse fibrosis gradually progress over time, whilst replacement fibrosis accumulates rapidly once first established. Following valve replacement, cellular hypertrophy regresses faster than diffuse fibrosis, but replacement fibrosis appears permanent and irreversible. I then proceeded to investigate T1 mapping measures in a large international multicentre cohort of patients with aortic stenosis scheduled for valve replacement. I showed that extracellular volume-based T1 mapping measures were comparable across centres and therefore confirmed that multicentre studies are feasible. Extracellular volume fraction was associated with a decompensating ventricle and emerged as a powerful independent predictor of all-cause mortality in this group. Finally, I investigated the use of novel hybrid magnetic resonance and positron emission tomography imaging in patients with aortic stenosis, showing that this technique is feasible and well-tolerated. I tested novel attenuation correction and motion correction methods and showed that this technique can offer multiparametric imaging of valve, myocardium and coronary arteries in a single scan. Conclusion I have defined the longitudinal changes in hypertrophy and myocardial fibrosis in aortic stenosis and validated extracellular volume measures as prognostic markers in this group. Moreover, I have described novel magnetic resonance and positron emission tomography techniques and their potential to aid the clinical assessment of patients with aortic stenosis

Global Strings and the Aharonov-Bohm Effect

When a fermion interacts with a global vortex or cosmic string a solenoidal "gauge" field is induced. This results in a non-trivial scattering cross-section. For scalars and non-relativistic fermions the cross-section is similar to that of Aharonov and Bohm, but with corrections. A cosmological example is compared to one in liquid He$^{3}$-A and important differences are discovered.Comment: 11 pages, DAMTP 93-5

Asthma in Vermont Dairy Farmers

Introduction. Although 5.4% of the Vermont population participates in agriculture as an occupation, little data exists on the prevalence of asthma in Vermont dairy farmers, due to inadequate sample sizes. Previous studies have shown dairy farmers are at risk of respiratory illness due to unique exposures intrinsic to their occupation. We conducted a study to assess the prevalence of asthma in dairy farmers in Vermont, to understand rates among this population and potential occupational risks.Methods. We distributed a paper survey modeled after previously-validated surveys, such as the BRFSS, to farmers at Vermont Farmer Bureau meetings, farmers markets, and individual farmers through Cabot Creamery. Out of 309 distributed surveys, we received 176 completed surveys for a response rate of 57%.Results. Self-reported asthma rate in dairy farmers was 21% (22% in dairy only farmers), with 90% of these cases reported as confirmed by a doctor. Of non-dairy farmers, 11% self-reported experiencing asthma. Farming activities associated with exacerbation of asthma symptoms were milking, prepping or cleaning bedding, and haying. 31% of dairy-only farmers reported symptom exacerbations due to these occupational triggers.Conclusions. The prevalence of asthma in Vermont dairy farmers is one of the highest reported rates in any Vermont occupation. Our data suggest that certain occupational exposures may increase risk of asthma and warrant further study; certain farming practices were associated with exacerbation of respiratory symptoms in farmers diagnosed with asthma. These findings and further research can assist in development of health care and preventive health measures for farmers.https://scholarworks.uvm.edu/comphp_gallery/1238/thumbnail.jp

The Testing of an Alternator

"Before a company which manufactures electrical machines allow them to leave the factory, each must undergo certain tests to make sure that there are no faults of design or workmanship and also ofttimes that they meet the specifications of the buyer. Four important tests are made, e.g. (1) no load and (2) load characteristics, (3) short circuit and (4) efficiency tests. To make a test cf a large machine loaded would take considerable rower. In practice the load characteristic is determined from the no-load and the short circuit curves."--p.

A Global Analog of Cheshire Charge

It is shown that a model with a spontaneously broken global symmetry can support defects analogous to Alice strings, and a process analogous to Cheshire charge exchange can take place. A possible realization in superfluid He-3 is pointed out.Comment: 24 pages (figures 1-4 included as uu-encoded tar files), CALT-68-1865 (Revised version: an expression (eq. 17) for global charge density is corrected; some typos and sign mismatches are removed.

Causality - Complexity - Consistency: Can Space-Time Be Based on Logic and Computation?

The difficulty of explaining non-local correlations in a fixed causal structure sheds new light on the old debate on whether space and time are to be seen as fundamental. Refraining from assuming space-time as given a priori has a number of consequences. First, the usual definitions of randomness depend on a causal structure and turn meaningless. So motivated, we propose an intrinsic, physically motivated measure for the randomness of a string of bits: its length minus its normalized work value, a quantity we closely relate to its Kolmogorov complexity (the length of the shortest program making a universal Turing machine output this string). We test this alternative concept of randomness for the example of non-local correlations, and we end up with a reasoning that leads to similar conclusions as in, but is conceptually more direct than, the probabilistic view since only the outcomes of measurements that can actually all be carried out together are put into relation to each other. In the same context-free spirit, we connect the logical reversibility of an evolution to the second law of thermodynamics and the arrow of time. Refining this, we end up with a speculation on the emergence of a space-time structure on bit strings in terms of data-compressibility relations. Finally, we show that logical consistency, by which we replace the abandoned causality, it strictly weaker a constraint than the latter in the multi-party case.Comment: 17 pages, 16 figures, small correction