Some investigations to compare the durability and performance of mechanical and porcine heart valve prostheses

The work reported in this thesis is an inherent part of research carried out in Edinburgh to assess the performance and durability of heart valve prostheses. Frcm 1975 to 1979 540 patients undergoing heart valve replacement in Edinburgh Royal Infirmary were entered into a randomised trial and received either a mechanical (Bjork-Shiley), or porcine heterograft (Hancock or Carpentier-Edwards) prosthesis. Starting in 1977 in the United States the Veterans Administration carried out a similar randomised trial on 575 patients. After a mean period of 5 years no significant advantage to any of the three prostheses was observed, although there were some differences in the results reported in the Edinburgh and the US trials and possible explanations for these are proposed.This thesis extends the analysis of the trial to a mean period of 10.5 years with respect to survival, and the incidence of reoperation, complications of anticoagulation, systemic embolism and bacterial endocarditis. It also presents a Doppler ultrasound comparison of the haemodynamic performance of the different valves in a subset of 102 patients.After this extended follow-up period we have again observed no difference in survival between those receiving a mechanical or porcine prosthesis. Reoperation for valve failure was necessary significantly more often in patients with porcine prostheses (53 patients) than in those with the Bjork-Shiley prosthesis (17 patients). This difference was almost entirely due to cusp failure of porcine prostheses occurring more than 5 years after implantation. An actuarial analysis of valve survival using reoperation or cardiac death as end-points showed significantly better valve survival for patients receiving the Bjork-Shiley prosthesis when all patients and the subgroup undergoing mitral valve replacement were considered, but not in the subgroup receiving an aortic valve replacement.All patients with Bjork-Shiley prostheses received longterm anticoagulation therapy, and bleeding complications were more frequent in this group. Death, reoperation, bleeding and complications of anticoagulation, .systemic embolism and bacterial endocarditis were taken as end points for an actuarial analysis of "event-free survival". There was a non-significant trend in favour of the Bjork-Shiley prosthesis when all patients and the subgroup undergoing mitral valve replacement were considered, but no discemable trend after aortic valve replacement.Doppler ultrasound techniques have been used to compare the haemodynamic performance of the Bjork-Shiley and porcine prostheses an average of 10 years after implantation in 102 patients enrolled in the Edinburgh trial. No significant difference in peak instantaneous or mean pressure gradient across the prosthesis was observed in patients who had undergone aortic or mitral valve replacement. There was however a significantly lower pressure half-time in patients with Bjork-Shiley compared with those with porcine mitral valve prostheses but this fell after exercise in those with porcine mitral prostheses, suggesting that this difference, observed at rest does not indicate better haemodynamic performance of the Bjork-Shiley prosthesis

Evidence for Partial Taylor Relaxation from Changes in Magnetic Geometry and Energy during a Solar Flare

Solar flares are powered by energy stored in the coronal magnetic field, a portion of which is released when the field reconfigures into a lower energy state. Investigation of sunspot magnetic field topology during flare activity is useful to improve our understanding of flaring processes. Here we investigate the deviation of the non-linear field configuration from that of the linear and potential configurations, and study the free energy available leading up to and after a flare. The evolution of the magnetic field in NOAA region 10953 was examined using data from Hinode/SOT-SP, over a period of 12 hours leading up to and after a GOES B1.0 flare. Previous work on this region found pre- and post-flare changes in photospheric vector magnetic field parameters of flux elements outside the primary sunspot. 3D geometry was thus investigated using potential, linear force-free, and non-linear force-free field extrapolations in order to fully understand the evolution of the field lines. Traced field line geometrical and footpoint orientation differences show that the field does not completely relax to a fully potential or linear force-free state after the flare. Magnetic and free magnetic energies increase significantly ~ 6.5-2.5 hours before the flare by ~ 10^31 erg. After the flare, the non-linear force-free magnetic energy and free magnetic energies decrease but do not return to pre-flare 'quiet' values. The post-flare non-linear force-free field configuration is closer (but not equal) to that of the linear force-free field configuration than a potential one. However, the small degree of similarity suggests that partial Taylor relaxation has occurred over a time scale of ~ 3-4 hours.Comment: Accepted for Publication in Astronomy & Astrophysics. 11 pages, 11 figure

Modelling The World : The Social Constructions Of Systems Analysts

This dissertation is concerned with a case study of system dynamics, a well-known simulation modelling methodology, and its implicit theory of social system behaviour. System dynamics is policy oriented and is directed towards the control and management of social systems. It originally evolved in the context of military systems and then the application of systems engineering to the problems of corporate management, but was later expanded to tackle the problems of urban decay, population growth, and environmental collapse. It is therefore now aimed at large scale social engineering. The aim of the dissertation is to take tools drawn largely from the sociology of knowledge in order t o provide a perspective on the development of this particular strand of the systems movement. We investigate the status of system dynamics as a cultural artefact which is both a product of social structures and a resource for mediating and reinforcing such structures. The dissertation is addressed to the systems community, but must also meet the academic standards of the sociology of knowledge. There are seven chapters. The first two deal with the background to system dynamics and with methodological aspects of the perspective adopted in our approach. The following two chapters examine system dynamics as a social construction: firstly, with special emphasis on the social development of the cultural context in which it evolved; and secondly, on the social experience and cosmology of the System Dynamics Group at MIT. The next two chapters deal with the social effects of system dynamics, particularly its role as a 'binding agent' in negotiating social consensus. The seventh and final chapter discusses our conclusions

Inherent variability of cancer-specific aneuploidy generates metastases.

BACKGROUND: The genetic basis of metastasis is still unclear because metastases carry individual karyotypes and phenotypes, rather than consistent mutations, and are rare compared to conventional mutation. There is however correlative evidence that metastasis depends on cancer-specific aneuploidy, and that metastases are karyotypically related to parental cancers. Accordingly we propose that metastasis is a speciation event. This theory holds that cancer-specific aneuploidy varies the clonal karyotypes of cancers automatically by unbalancing thousands of genes, and that rare variants form new autonomous subspecies with metastatic or other non-parental phenotypes like drug-resistance - similar to conventional subspeciation. RESULTS: To test this theory, we analyzed the karyotypic and morphological relationships between seven cancers and corresponding metastases. We found (1) that the cellular phenotypes of metastases were closely related to those of parental cancers, (2) that metastases shared 29 to 96% of their clonal karyotypic elements or aneusomies with the clonal karyotypes of parental cancers and (3) that, unexpectedly, the karyotypic complexity of metastases was very similar to that of the parental cancer. This suggests that metastases derive cancer-specific autonomy by conserving the overall complexity of the parental karyotype. We deduced from these results that cancers cause metastases by karyotypic variations and selection for rare metastatic subspecies. Further we asked whether metastases with multiple metastasis-specific aneusomies are assembled in one or multiple, sequential steps. Since (1) no stable karyotypic intermediates of metastases were observed in cancers here and previously by others, and (2) the karyotypic complexities of cancers are conserved in metastases, we concluded that metastases are generated from cancers in one step - like subspecies in conventional speciation. CONCLUSIONS: We conclude that the risk of cancers to metastasize is proportional to the degree of cancer-specific aneuploidy, because aneuploidy catalyzes the generation of subspecies, including metastases, at aneuploidy-dependent rates. Since speciation by random chromosomal rearrangements and selection is unpredictable, the theory that metastases are karyotypic subspecies of cancers also explains Foulds\u27 rules, which hold that the origins of metastases are abrupt and that their phenotypes are unpredictable

Wintertime losses of ozone in high northern latitudes

Total column ozone data over the past 22 to 30 years from ground-based Dobson and filter ozonometer stations between 30 N and 80 N are analyzed for residual trends remaining after allowance for the known geophysical variations corresponding to: (1) the change of seasons; (2) the quasi-biennial oscillation; and (3) the 11-year solar sunspot cycle. Examination of the data from several ground stations between 45 and 55 N indicated a seasonal difference in the long-term ozone series, with statistically significant losses in several winter months. Accordingly, the data from individual stations were analyzed with multiple regression analysis, seeking trends on a monthly basis after allowance for the known geophysical cycles. Previous statistical analyses were conducted as tests of 1-D model calculations which do not show any differences with the seasons, and any trend toward change in ozone concentrations is expressed in a yearly trend without seasonal variation. Such a model is inappropriate for calculations with a data set which exhibits a pronounced tendency toward seasonal differences in the trends. Comparisons with model calculations then require 2-D models into which seasonal and latitudinal differences can easily be programmed