No description available.

<p>Several extensions to the Standard Model predict the existence of charged Higgs bosons. This thesis describes the search for such a particle using the data collected by the DELPHI detector at the Large Electron Positron (LEP) collider at the European laboratory for particle physics (CERN) in Geneva, Switzerland. </p><p>In <i>e</i>⁺<i>e </i>^-collisions charged Higgs bosons are predicted to be produced in pairs via an intermediate photon or Z⁰ boson. In the two Higgs doublet model (2HDM) the production cross section for a pair of charged Higgs bosons depends only on the centre of mass energy of the collision and the mass of the charged Higgs boson. </p><p>Higgs bosons decay to the heaviest particles kinematically allowed. For a charged Higgs boson with a mass that can be produced at the LEP collider this means either a <i>cs</i> quark pair or a <i>τυ</i>_t lepton pair. The branching ratio between these decay channels depends on the parameters of the model. </p><p>No statistically significant signal compatible with a charged Higgs boson was found. Using the predicted production cross sections from the 2HDM the existence of a charged Higgs boson with a mass lower than 73.8 GeV/<i>c</i>² has been excluded at 95% confidence level independently of the decay branching ratios of the charged Higgs boson. </p>

The aim of the present thesis was to evaluate sonographic methods for investigation of the chronic painful Achilles tendon. In a prospective study on patients with chronic painful mid-portion Achilles tendinosis, grey-scale ultrasound (US) showed a decreased tendon thickness and a “normalized” structure in the majority of patients successfully treated with eccentric calf-muscle training. By combining US with colour Doppler examination (CDV), a neovascularisation was shown in the region with structural tendon changes in all painful tendons, but not in any of the pain-free normal tendons. In a small pilot study, the sclerosing agent Polidocanol was injected towards the neovessels under US and CDV guidance. The majority of the patients became painfree and had no remaining neovessels, while the patients with remaining pain had remaining neovessels. The combined findings from US, immuno-histochemical analyses of biopsies, and diagnostic injections, showed that the patients were temporarily pain-free after US and CDV guided injections of local anaesthesia towards the region with neovessels, and biopsies from the region with tendon changes and neovascularisation showed nerve structures in close relation to blood vessels. The presence of neovessels was shown also in patients with chronic pain in the Achilles tendon insertion, and it was found that treatment with sclerosing injections cured the pain in the majority of patients. A good result of treatment was associated with no remaining neovessels. In a prospective study on patients with chronic mid-portion Achilles tendinosis treated with eccentric training, CDV after treatment showed no remaining neovessels in the majority of the pain-free patients. In the patients with remaining tendon pain there were remaining neovessels. In conclusion, the findings in this thesis indicate that neovessels and accompanying nerves might be the source of chronic Achilles tendon pain. Sclerosing injections towards the neovessels, and eccentric training, seem to have a potential to cure the pain.

No description available.

Several extensions to the Standard Model predict the existence of charged Higgs bosons. This thesis describes the search for such a particle using the data collected by the DELPHI detector at the Large Electron Positron (LEP) collider at the European laboratory for particle physics (CERN) in Geneva, Switzerland. In e+e - collisions charged Higgs bosons are predicted to be produced in pairs via an intermediate photon or Z0 boson. In the two Higgs doublet model (2HDM) the production cross section for a pair of charged Higgs bosons depends only on the centre of mass energy of the collision and the mass of the charged Higgs boson. Higgs bosons decay to the heaviest particles kinematically allowed. For a charged Higgs boson with a mass that can be produced at the LEP collider this means either a cs quark pair or a τυt lepton pair. The branching ratio between these decay channels depends on the parameters of the model. No statistically significant signal compatible with a charged Higgs boson was found. Using the predicted production cross sections from the 2HDM the existence of a charged Higgs boson with a mass lower than 73.8 GeV/c2 has been excluded at 95% confidence level independently of the decay branching ratios of the charged Higgs boson.

<p>Biological treatment optimization aim at improving radiation therapy by accounting for the radiobiological tumour and normal tissues response properties when optimizing the dose delivery. Generally traditional methods, using only dosimetrical measures, disregard the nonlinear radiation response of different tumours and normal tissues. The accumulated knowledge on tissue response to radiation, in the form of more accurate dose response relations, cell survival models and their associated biological parameters, alongside with the tools for biological treatment plan optimization, has allowed the present investigation on the potential merits of biologically based treatment optimization in radiation therapy.</p><p>With a more widespread implementation of intensity modulated radiation therapy in the clinic, there is an increasing demand for faster and safer treatment delivery techniques. In this thesis biological treatment plan optimization, using the probability to achieve complication free tumour control as the quantifier for treatment outcome, was applied to radiation therapy of early breast cancer and advanced cervix cancer. It is shown that very conformal dose distributions can generally be produced with 3 or 4 optimally orientated coplanar intensity modulated beams, without having clinically significant losses in treatment outcome from the optimal dose distribution.</p><p>By using exhaustive search methods, the optimal coplanar beam directions for intensity modulated photon beams for early breast cancer and the optimal non-coplanar directions for an advanced cervix cancer were investigated. Although time consuming, exhaustive search methods have the advantage of revealing most features involving interactions between a small number of beams and how this may influence the treatment outcome. Thus phase spaces may serve as a general database for selecting an almost optimal treatment configuration for similar patients. Previous knowledge acquired with physically optimized uniform beam radiation therapy may not apply when intensity modulated biological optimization is used. Thus unconventional treatment directions were sometimes found.</p>

<p>One of the main problems in curing cancer resides in the different microenvironment existing in tumours compared to the normal tissues. The mechanisms of failure are different for radiotherapy and chemotherapy, but they all relate to the poor blood supply known to exist in tumours. It is therefore very important to know the tumour microenvironmental conditions in order to devise techniques that will overcome the problems and will therefore improve the result of the treatment.</p><p>The aims of the thesis were the modelling of tumour oxygenation and the simulation of polarographic oxygen measurements in order to assess and possibly to improve the accuracy of the electrode in measuring tumour oxygenation. It also aimed to evaluate the implications of tumour microenvironment for the radiotherapy outcome.</p><p>The project used theoretical modelling as the main tool. The processes of oxygen diffusion and consumption were described mathematically for different conditions, the result being very accurate distributions of oxygen in tissues. A first simple model of tissue oxygenation was based on the oxygen diffusion around a single blood vessel. A more complex model built from the basic physical processes and measurable parameters allowed the simulation of realistical tissues with heterogeneous vasculature. This model also allowed the modelling of the two types of hypoxia known to appear in tumours and their influence on the tumour microenvironment. The computer simulation of tissues was also used for assessing the accuracy of the polarographic technique for measuring tumour oxygenation.</p><p>The results of this study have shown that it is possible to model theoretically the tissue oxygenation starting from the basic physical processes. The particular application of our theoretical simulation to the polarographic oxygen electrode has shown that this experimental method does not give the oxygen values in individual cells. Because the electrode measures the average oxygenation in a relatively large tissue volume, the resulting oxygen distributions are different from the real ones and the extreme high and low values are not detected. It has further been found that the polarographic electrode cannot make distinction between various types of hypoxia existing in tumours, the geometrical distribution of the hypoxic cells influencing mostly the accuracy of the measurement.</p><p>It was also shown that because of the averaging implied by the measurement process, electrode results should not be used directly to predict the response to radiation. Thus, the differences between the predictions in clinical tumour control obtained from the real or the measured oxygenations are of the order of tens of percents in absolute value. A method to improve the accuracy of the electrode, i.e. to improve the correlation between the results of the measurements and the actual tissue oxygenation, was proposed.</p><p>In conclusion, theoretical modelling has been shown to be a very powerful tool for predicting the outcome of radiotherapy and it has the advantage of describing the tumour oxygenation in the least invasive manner. Furthermore it allows the investigation of the invasiveness and the accuracy of various experimental methods.</p>

<p>The increasing demand for characterization of nuclear fuel, both from an operator and authority point of view, motivates the development of new experimental and, preferable, non-destructive methods. In this thesis, some methods based on nuclear spectroscopic techniques are presented.</p><p>Various parameters of irradiated fuel are shown to be determined with high accuracy and confidence by utilizing gamma-ray scanning, tomography and passive neutron assay.</p><p>Specifically, fuel parameters relevant for a secure storage of spent nuclear fuel in a long-term repository, such as e.g. burnup and decay heat, are shown to be determined with adequate accuracy. The techniques developed are expected to be implemented in the planned encapsulation facility in Sweden.</p><p>Also, a device for tomographic measurements of the spatial distribution of thermal power in nuclear fuel assemblies has been built, tested and evaluated. The device utilizes single photon emission computed tomography (SPECT) in order to reconstruct the gamma-ray source distribution within a fuel assembly. The device is expected to be an important tool for validating reactor core simulators regarding new fuel designs.</p><p>For safeguards purposes, two experimental methods for verifying the integrity, i.e. the possible loss of fissile material from a nuclear fuel assembly, are presented. Verification of integrity is shown to be possible on an individual fuel rod level.</p>

<p>Tumour targeted radiotherapy is an appealing approach for treatment of disseminated tumour cells. A targeting agent that specifically binds to a structure on tumour cells is then used to transport therapeutically relevant radionuclides. The epidermal growth factor receptor, EGFR, is overexpressed on tumour cells in several malignancies, e.g. highly malignant gliomas. In this thesis, three types of radiolabelled EGF-conjugates, aimed for targeting to EGFR-expressing tumour cells, were developed and studied: EGF-dextran labelled with ¹²⁵I, EGF labelled with ²¹¹At, and two EGF-chelates, DTPA-EGF and Bz-DTPA-EGF, labelled with the radioactive metals ¹¹¹In and ¹⁷⁷Lu. </p><p>The targeting properties of radioiodinated EGF-dextran were first studied in cultured glioma cells. Radioiodine coupled to the dextran part of EGF-dextran was retained in cells appreciably longer than radioiodine coupled to EGF. This can give about 100 times increased radiation dose to tumour cells.</p><p>Targeting with ²¹¹At-EGF was investigated in combination with the tyrosine kinase inhibitor gefitinib (Iressa™, ZD1839). The uptake of ²¹¹At-EGF in EGFR-expressing tumour cells increased with increasing gefitinib concentrations. This was the case for both gefitinib-resistant and gefitinib-sensitive cell lines. The effect of the combined treatment on cell survival, however, differed between the cell lines in an unexpected way. In gefitinib resistant cells, combined treatment decreased cell survival approximately 3.5 times relative to ²¹¹At-EGF treatment alone. In gefitinib sensitive cells, however, combined treatment increased the cell survival (i.e. a protective effect).</p><p>The EGF-chelates studied ([¹¹¹In]DTPA-EGF, [¹¹¹In]Bz-DTPA-EGF and [¹⁷⁷Lu]Bz-DTPA-EGF) all bound specifically with high affinity (K_d≈2 nM) to EGFR on cultured glioma cells. They were internalised after binding, and the cellular retention of radionuclides was high (60% remained after 45 h). A biodistribution study in mice showed that liver and kidneys accumulated a majority of the radioactivity. The EGF-chelates bound EGFR specifically also <i>in vivo</i>. A tumour-to-blood ratio of 25 was achieved in a preliminary study.</p>

<p>The development of digital detectors for X-ray imaging in medical diagnostics receives an increasing amount of attention. The detector under development at the Department of Radiation Sciences at Uppsala University is a hybrid pixel detector, which consists of a semiconductor sensor mounted onto a readout chip. The readout chip is capable of performing photon counting and has an externally adjustable threshold.</p><p>A simulation tool for the detector and a model applying the linear-systems transfer theory to X-ray hybrid pixel detectors have been developed. Also a characterization of the readout chip has been done. In order to estimate the potential of the detector for diagnostic radiology, we investigate the image quality using the spatial frequency dependent detective quantum efficiency (DQE). By means of the detector simulations, the influence of threshold setting, noise sources, level of exposure and charge sharing on the DQE have been studied. By means of the linear-systems theory, a single analytical expression is provided to obtain the DQE of a hybrid pixel detector.</p><p>The method developed in this thesis will make it possible to optimize a detector design according to a particular medical application. It will also permit modifications and new features to be included without having to construct a full detector system.</p>