Iodine Brachytherapy for Large Uveal Melanomas

Uveal melanoma is the most common primary intraocular malignancy in adults. Vision in the affected eye is threatened by both the tumor and side-effects from the treatments currently available. Poor prognosis for saving vision increases with tumor size and, consequently, enucleation has been the treatment of choice for large uveal melanomas in most centers. However, increasing evidence suggests that no survival benefit is gained (nor lost) by enucleation as compared to eye-conserving methods. The Helsinki University Eye Hospital has since 1990 offered episcleral iodine-125 plaque brachytherapy (IBT) for all patients unwilling to undergo enucleation for a large uveal melanoma. The primary aim of this study was to assess survival, local tumor recurrence and preservation of the eye and vision after IBT in a population-based series of 97 patients with uveal melanomas classified as large by the Collaborative Ocular Melanoma Study (COMS) criteria. Further aims included reporting the incidence of side-effects and assessing the role of intraocular dose distribution and clinical risk factors in their development. Finally, means to improve the current treatment were investigated by using computer models to compare existing plaques with collimating ones and by comparing the outcome of a subgroup of 54 IBT patients with very thick tumors with 33 patients with similarly-sized tumors managed with transscleral local resection (TSR) in Liverpool, United Kingdom. Kaplan-Meier estimates of all-cause and melanoma-specific survival at 5 years after IBT were 62% and 65%, respectively, and visually comparable with the survival experience of patients reported after enucleation by the COMS. Local recurrence developed in 6% of eyes and 84% of eyes were conserved at 5 years. Visual prognosis was guarded with 11% avoiding loss of 20/70 vision and 26% avoiding loss of 20/400 vision in the tumor eye at 2 years. Large tumor height and short distance from the posterior pole were independently associated with loss of vision. Using cumulative incidence analysis to account for competing risks, such as enucleation and metastatic death, the 5-year incidence of cataract after IBT was 79%, glaucoma 60%, optic neuropathy 46%, maculopathy 52%, persistent or recurring retinal detachment (RD) 25%, and vitreous hemorrhage 36%. In multivariate competing risks regression models, increasing tumor height was associated with cataract, iris neovascularization and RD. Maculopathy and optic neuropathy were associated with distance from the tumor to the respective structure. Median doses to the tumor apex, macula and optic disc were 81 Gy (range, 40-158), 79 Gy (range, 12-632), and 83 Gy (range, 10-377), respectively. Dose to the optic disc was independently associated with optic neuropathy, and both dose to the optic disc and dose to the macula predicted vision loss after IBT. Simulated treatment using collimating plaques resulted in clinically meaningful reduction in both optic disc (median reduction, 30 Gy) and macular (median reduction, 36 Gy) doses as compared to the actual treatment with standard plaques. In the subgroup of patients with uveal melanomas classified as large because of tumor height, cumulative incidence analysis revealed that while long-term preservation of 20/70 vision was rare after both IBT and TSR, preservation of 20/400 vision was better after TSR (32% vs. 5% at 5 years). In multivariate logistic regression models, TSR was independently associated with better preservation of 20/400 vision (OR 0.03 at 2 years, P=0.005) No cases of secondary glaucoma were observed after TSR and optic neuropathy was rare. However, local tumor recurrence was more common after TSR than it was after IBT (Cumulative incidence 41% vs. 7% at 5 years, respectively). In terms of survival, IBT seems to be a safe alternative to enucleation in managing large uveal melanomas. Local tumor control is no worse than with medium-sized tumors and the chances of avoiding secondary enucleation are good. Unfortunately, side-effects from radiotherapy are frequent, especially in thick tumors, and long-term prognosis of saving vision is consequently guarded. Some complications can be limited by using collimating plaques and by managing uveal melanomas that are large because of tumor height with TSR instead of IBT. However, the patient must be willing to accept a substantial risk of local tumor recurrence after TSR and it is best suited for cases in which the preservation of vision in the tumor eye is critical.

Dynamics of free-running, pump-modulated and coupled semiconductor and solid-state lasers

The output of a laser is a high frequency propagating electromagnetic field with superior coherence and brightness compared to that emitted by thermal sources. A multitude of different types of lasers exist, which also translates into large differences in the properties of their output. Moreover, the characteristics of the electromagnetic field emitted by a laser can be influenced from the outside, e.g., by injecting an external optical field or by optical feedback. In the case of free-running solitary class-B lasers, such as semiconductor and Nd:YVO4 solid-state lasers, the phase space is two-dimensional, the dynamical variables being the population inversion and the amplitude of the electromagnetic field. The two-dimensional structure of the phase space means that no complex dynamics can be found. If a class-B laser is perturbed from its steady state, then the steady state is restored after a short transient. However, as discussed in part (i) of this Thesis, the static properties of class-B lasers, as well as their artificially or noise induced dynamics around the steady state, can be experimentally studied in order to gain insight on laser behaviour, and to determine model parameters that are not known ab initio. In this Thesis particular attention is given to the linewidth enhancement factor, which describes the coupling between the gain and the refractive index in the active material. A highly desirable attribute of an oscillator is stability, both in frequency and amplitude. Nowadays, however, instabilities in coupled lasers have become an active area of research motivated not only by the interesting complex nonlinear dynamics but also by potential applications. In part (ii) of this Thesis the complex dynamics of unidirectionally coupled, i.e., optically injected, class-B lasers is investigated. An injected optical field increases the dimensionality of the phase space to three by turning the phase of the electromagnetic field into an important variable. This has a radical effect on laser behaviour, since very complex dynamics, including chaos, can be found in a nonlinear system with three degrees of freedom. The output of the injected laser can be controlled in experiments by varying the injection rate and the frequency of the injected light. In this Thesis the dynamics of unidirectionally coupled semiconductor and Nd:YVO4 solid-state lasers is studied numerically and experimentally.

Studies of Earth Dynamics with the Superconducting Gravimeter

The superconducting (or cryogenic) gravimeter (SG) is based on the levitation of a super­conducting sphere in a stable magnetic field created by current in superconducting coils. Depending on frequency, it is capable of detecting gravity variations as small as 10-11ms-2. For a single event, the detection threshold is higher, conservatively about 10-9 ms-2. Due to its high sensitivity and low drift rate, the SG is eminently suitable for the study of geodynamical phenomena through their gravity signatures. I present investigations of Earth dynamics with the superconducting gravimeter GWR T020 at Metsähovi from 1994 to 2005. The history and key technical details of the installation are given. The data processing methods and the development of the local tidal model at Metsähovi are presented. The T020 is a part of the worldwide GGP (Global Geodynamics Project) network, which consist of 20 working station. The data of the T020 and of other participating SGs are available to the scientific community. The SG T020 have used as a long-period seismometer to study microseismicity and the Earth s free oscillation. The annual variation, spectral distribution, amplitude and the sources of microseism at Metsähovi were presented. Free oscillations excited by three large earthquakes were analyzed: the spectra, attenuation and rotational splitting of the modes. The lowest modes of all different oscillation types are studied, i.e. the radial mode 0S0, the "football mode" 0S2, and the toroidal mode 0T2. The very low level (0.01 nms-1) incessant excitation of the Earth s free oscillation was detected with the T020. The recovery of global and regional variations in gravity with the SG requires the modelling of local gravity effects. The most important of them is hydrology. The variation in the groundwater level at Metsähovi as measured in a borehole in the fractured bedrock correlates significantly (0.79) with gravity. The influence of local precipitation, soil moisture and snow cover are detectable in the gravity record. The gravity effect of the variation in atmospheric mass and that of the non-tidal loading by the Baltic Sea were investigated together, as sea level and air pressure are correlated. Using Green s functions it was calculated that a 1 metre uniform layer of water in the Baltic Sea increases the gravity at Metsähovi by 31 nms-2 and the vertical deformation is -11 mm. The regression coefficient for sea level is 27 nms-2m-1, which is 87% of the uniform model. These studies are associated with temporal height variations using the GPS data of Metsähovi permanent station. Results of long time series at Metsähovi demonstrated high quality of data and correctly carried out offsets and drift corrections. The superconducting gravimeter T020 has been proved to be an eminent and versatile tool in studies of the Earth dynamics.

Open and closed boundaries in large-scale convective dynamos

Earlier work has suggested that large-scale dynamos can reach and maintain equipartition field strengths on a dynamical time scale only if magnetic helicity of the fluctuating field can be shed from the domain through open boundaries. To test this scenario in convection-driven dynamos by comparing results for open and closed boundary conditions. Three-dimensional numerical simulations of turbulent compressible convection with shear and rotation are used to study the effects of boundary conditions on the excitation and saturation level of large-scale dynamos. Open (vertical field) and closed (perfect conductor) boundary conditions are used for the magnetic field. The contours of shear are vertical, crossing the outer surface, and are thus ideally suited for driving a shear-induced magnetic helicity flux. We find that for given shear and rotation rate, the growth rate of the magnetic field is larger if open boundary conditions are used. The growth rate first increases for small magnetic Reynolds number, Rm, but then levels off at an approximately constant value for intermediate values of Rm. For large enough Rm, a small-scale dynamo is excited and the growth rate in this regime increases proportional to Rm^(1/2). In the nonlinear regime, the saturation level of the energy of the mean magnetic field is independent of Rm when open boundaries are used. In the case of perfect conductor boundaries, the saturation level first increases as a function of Rm, but then decreases proportional to Rm^(-1) for Rm > 30, indicative of catastrophic quenching. These results suggest that the shear-induced magnetic helicity flux is efficient in alleviating catastrophic quenching when open boundaries are used. The horizontally averaged mean field is still weakly decreasing as a function of Rm even for open boundaries.

The International Large Detector: Letter of Intent

The International Large Detector (ILD) is a concept for a detector at the International Linear Collider, ILC. The ILC will collide electrons and positrons at energies of initially 500 GeV, upgradeable to 1 TeV. The ILC has an ambitious physics program, which will extend and complement that of the Large Hadron Collider (LHC). A hallmark of physics at the ILC is precision. The clean initial state and the comparatively benign environment of a lepton collider are ideally suited to high precision measurements. To take full advantage of the physics potential of ILC places great demands on the detector performance. The design of ILD is driven by these requirements. Excellent calorimetry and tracking are combined to obtain the best possible overall event reconstruction, including the capability to reconstruct individual particles within jets for particle ow calorimetry. This requires excellent spatial resolution for all detector systems. A highly granular calorimeter system is combined with a central tracker which stresses redundancy and efficiency. In addition, efficient reconstruction of secondary vertices and excellent momentum resolution for charged particles are essential for an ILC detector. The interaction region of the ILC is designed to host two detectors, which can be moved into the beam position with a push-pull scheme. The mechanical design of ILD and the overall integration of subdetectors takes these operational conditions into account.

Essays on the Costs and Benefits of Large Shareholders in Corporate Governance (summary section only)

“Corporate governance deals with the ways in which suppliers of finance to firms assure themselves of getting a return on their investment” (Shleifer and Vishny (1997, p. 737). According to La Porta et al. (1999), research in corporate finance relevant for most countries should focus on the incentives and capabilities of controlling shareholders to treat themselves preferentially at the expense of minority shareholders. Accordingly, this thesis sets out to answer a number of research questions regarding the role of large shareholders in public firms that have received little attention in the literature so far. A common theme in the essays stems from the costs and benefits of individual large-block owners and the role of control contestability from the perspective of outside minority shareholders. The first essay empirically examines whether there are systematic performance differences between family controlled and nonfamily controlled firms in Western Europe. In contrast to the widely held view that family control penalizes firm value, the essay shows that publicly traded family firms have higher performance than comparable firms. In the second essay, we present both theoretical and empirical analysis on the effects of control contestability on firm valuation. Consistent with the theoretical model, the empirical results show that minority shareholders benefit from a more contestable control structure. The third essay explores the effects of individual large-block owners on top management turnover and board appointments in Finnish listed firms. The results indicate that firm performance is an important determinant for management and board restructurings. For certain types of turnover decisions the corporate governance structure influences the performance / turnover sensitivity. In the fourth essay, we investigate the relation between the governance structure and dividend policy in Finnish listed firms. We find evidence in support of the outcome agency model of dividends stating that lower agency conflicts should be associated with higher dividend payouts.

The Evolving Roles of the Human Resource Function: Understanding Role Changes in the Context of Large-Scale Mergers

The human resource (HR) function is under pressure both to change roles and to play a large variety of roles. Questions of change and development in the HR function become particularly interesting in the context of mergers and acquisitions when two corporations are integrated. The purpose of the thesis is to examine the roles played by the HR function in the context of large-scale mergers and thus to understand what happens to the HR function in such change environments, and to shed light on the underlying factors that influence changes in the HR function. To achieve this goal, the study seeks first to identify the roles played by the HR function before and after the merger, and second, to identify the factors that affect the roles played by the HR function. It adopts a qualitative case study approach including ten focal case organisations (mergers) and four matching cases (non-mergers). The sample consists of large corporations originating from either Finland or Sweden. HR directors and members of the top management teams within the case organisations were interviewed. The study suggests that changes occur within the HR function, and that the trend is for the HR function to become increasingly strategic. However, the HR function was found to play strategic roles only when the HR administration ran smoothly. The study also suggests that the HR function has become more versatile. An HR function that was perceived to be mainly administrative before the merger is likely after the merger to perform some strategically important activities in addition to the administrative ones. Significant changes in the roles played by the HR function were observed in some of the case corporations. This finding suggests that the merger integration process is a window of opportunity for the HR function. HR functions that take a proactive and leading role during the integration process might expand the number of roles played and move from being an administrator before the merger to also being a business partner after integration. The majority of the HR functions studied remained mainly reactive during the organisational change process and although the evidence showed that they moved towards strategic tasks, the intra-functional changes remained comparatively small in these organisations. The study presents a new model that illustrates the impact of the relationship between the top management team and the HR function on the role of the HR function. The expectations held by the top management team for the HR function and the performance of the HR function were found to interact. On a dimension reaching from tactical to strategic, HR performance is likely to correspond to the expectations held by top management.

Managers Talk about Gender: What Managers in Large Transnational Corporations Say about Gender Policies, Structures and Practices

Mainstream research on management generally continues to ignore gender relations. Even so, over recent years there has been a major growth of international research on gender relations in organizations. Yet, most of this has focused on gender relations in lower or middle levels rather than at the apex of the organization. This book draws on research on gender policies, structures and practices of management in large Finnish corporations. It builds on earlier survey work of gender policies in the 100 largest corporations in Finland, to examine, through qualitative interviews, more detailed gendered processes in seven selected corporations. These represent corporations that are ‘relatively active’, ‘moderately active’, and ‘not active’ in relation to gender equality. Key issues include contrasts between formal policies and organizational practices; different corporate contexts and individual managers’ views; definition and scope of gender policy; and the relation of gender policies and diversity policy. This focus on gender policies is understood and located within organizational structures, most obviously gendered corporate hierarchies. Important structures include national context in relation to transnationalization, relations of headquarters and subsidiaries, and interrelations of management, policy development and policy implementation. Gender relations in practice and gender practices are considered in more detail. These women and men managers operate at the intersections of gendered transnational managerial work, careers and family-type relations, including marriage and children, or lack thereof. Women and men managers may be part of the same management levels or management teams, but have totally different family-type situations and gendered experiences. Interconnections of management, domestic life and transnationalizations are intensely gendered matters. The debate on the public/private continues to be important for both gender relations and organizational relations, but complicated through transnationalizations. The modern transnational corporation is considered in terms of gender divisions and gender power, with particular reference to top management. The concluding discussion notes implications for research and policy.

Modelling the dynamics of a large sea area

Yhteenveto: Laajan merialueen dynamiikan mallintaminen