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>It has been observed that the radiation response of a cell line may positively correlate with baseline levels of reactive oxygen species (ROS) generation, which is facilitated, in part, by the function ofNADPH oxidase membrane proteins. Apocynin has been successfully used to inhibit ROS generation via NADPH oxidase for other uses. Here, the effectiveness of apocynin to improve sensitivity to radiation in the MATLyLu cell line was examined. MATLyLu-implanted Cop/Hsd rats undergoing lOGy/SfX radiation treatment demonstrated improved tumour control, as measured by survival time (to predetennined endpoints), when given apocynin orally throughout their radiation treatment, but not when given apocynin only before radiation. Rats given apocynin without radiation did not demonstrate improved survival over controls. MA TLyLu cells given apocynin in vitro, however, did not demonstrate improved response to radiation or a reduction in baseline ROS production on a per cell basis, and apocynin was found to inhibit growth when given alone. These contradictory in vivo and in vitro findings may be explained by certain proposed mechanisms of action for apocynin which requires it to be first synthesized into its dimer, diapocynin, before it will inhibit NADPH oxidase, and this synthesis may occur during ingestion. Further investigations with diapocynin and the MATLyLu cell line are required. Therefore the mechanism is uncertain, but it was concluded that apocynin and radiation administered together in vivo improves radiation response as compared to either treatment alone.</p> / Master of Science (MS)

<p>Scanned proton beams offer the possibility to take full advantage of the dose deposition properties of proton beams, i.e. the limited range and sharp peak at the end of the range, the Bragg peak. By actively scanning the proton beam, laterally by scanning magnets and longitudinally by shifting the energy, the position of the Bragg peak can be controlled in all three dimensions, thereby enabling high dose delivery to the target volume only. A typical scanned proton beam line consists of a pair of scanning magnets to perform the lateral beam scanning and possibly a range shifter and a multi-leaf collimator (MLC). Part of this thesis deals with the development of control, supervision and verification methods for the scanned proton beam line at the The Svedberg laboratory in Uppsala, Sweden. </p><p>Radiotherapy is preceded by treatment planning, where one of the main objectives is predicting the dose to the patient. The dose is calculated by a dose calculation engine and the accuracy of the results is of course dependent on the accuracy and sophistication of the transport and interaction models of the dose engine itself. But, for the dose distribution calculation to have any bearing on the reality, it needs to be started with relevant input in accordance with the beam that is emitted from the treatment machine. This input is provided by the beam model. As such, the beam model is the link between the reality (the treatment machine) and the treatment planning system. The beam model contains methods to characterise the treatment machine and provides the dose calculation with the reconstructed beam phase space, in some convenient representation. In order for a beam model to be applicable in a treatment planning system, its methods have to be general. </p><p>In this thesis, a beam model for a scanned proton beam is developed. The beam model contains models and descriptions of the beam modifying elements of a scanned proton beam line. Based on a well-defined set of generally applicable characterisation measurements, ten beam model parameters are extracted, describing the basic properties of the beam, i.e. the energy spectrum, the radial and the angular distributions and the nominal direction. Optional beam modifying elements such as a range shifter and an MLC are modelled by dedicated Monte Carlo calculation algorithms. The algorithm that describes the MLC contains a parameterisation of collimator scatter, in which the rather complex phase space of collimator scattered protons has been parameterised by a set of analytical functions. </p><p>Dose calculations based on the phase space reconstructed by the beam model are in good agreement with experimental data. This holds both for the dose distribution of the elementary pencil beam, reflecting the modelling of the basic properties of the scanned beam, as well as for complete calculations of collimated scanned fields.</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>