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Coming theses from other universities

  • Intervening in a social world : An evaluation of an alcohol prevention programme in a Swedish workplace context Author: Devy Lysandra Elling Link: Publication date: 2022-05-18 09:00

    A sizeable portion of hazardous alcohol consumers are found in the workforce, suggesting that the workplace could provide opportunities for preventing and reducing hazardous alcohol use at an early stage. One such intervention is the multi-component alcohol prevention programme, ‘APMaT’ (Alcohol Policy and Managers’ skills Training), designed and delivered by Alna, an organisation that provides services to prevent harmful behaviours in Swedish workplaces. This thesis is a programme evaluation of APMaT, assessing its effectiveness through survey data at the managerial and employee levels.

    Study I described the sociodemographic, work-, and health-related characteristics of managers relative to their inclination to intervene and organisational alcohol policy knowledge. Moreover, the association between managers’ inclination to intervene and knowledge about organisational alcohol policy was examined. The number of supervised employees was strongly associated with both the inclination to intervene and alcohol policy knowledge, and a graded positive association was found between managers’ inclination to intervene and alcohol policy knowledge. The findings implied that managerial characteristics may play a role in potential actions to initiate early alcohol interventions.

    Study II evaluated the effectiveness of APMaT, focusing on changes in the inclination to intervene at an early stage among managers at one-year follow-up. The findings suggested that APMaT is somewhat effective in increasing managers’ inclination to initiate an intervention by increasing their confidence in initiating a dialogue with employees, which may increase the likelihood of initiating an intervention at an early stage.

    Study III further assessed the effectiveness of APMaT by examining changes in the risk of hazardous alcohol use among employees at one-year follow-up. The study did not provide strong empirical evidence in support of the effectiveness of APMaT regarding the reduction of hazardous alcohol use within the given follow-up time.

    Given the mixed support for the effectiveness provided by Studies II and III, Study IV described managers’ perceived barriers in the dissemination of their organisational alcohol policy. This dissemination was an important component of APMaT because all managers were expected to facilitate its implementation throughout the workplace. Uncertainties and a variety of perceived organisational obstacles were reported by the managers to have hindered the dissemination of the organisational alcohol policy.

    This thesis highlights the complexity of delivering and implementing an intervention in a complex and dynamic setting, such as the workplace. The findings suggested that the investigated intervention, APMaT, might be effective in changing attitudes among managers, whereas no concrete effects on employees’ hazardous alcohol use could be demonstrated. Nevertheless, the studies contributed with knowledge to the development of prospective workplace prevention programmes.

  • Microgels as drug delivery vehicles : loading and release of amphiphilic drugs Author: Yassir Al-Tikriti Link: Publication date: 2022-05-17 14:36

    Polyelectrolyte microgels are used as delivery vehicles for amphiphilic drugs in, e.g., treatments of liver cancer by a method called trans-arterial chemoembolization. The thesis deals with fundamental properties of such delivery systems related to the self-assembling properties of the drug molecules and their interaction with the charged polymer network of the microgel. The main objective was to establish mechanistic models describing the loading and release of drugs under relevant conditions. For that purpose experimental techniques providing thermodynamic, compositional and microstructural information were used to elucidate how the kinetics depend on the stability of the drug self-assemblies and the volume response of the microgels. Micromanipulator-assisted microscopy studies showed that negatively charged microgels phase separated during loading and release of cationic amphiphilic drugs. At intermediate loading levels the drug aggregates and part of the network formed a collapsed phase coexisting with a swollen, drug-lean phase. In particular, during release in a medium of physiological ionic strength, the drug-lean phase formed a depletion layer (shell) surrounding a drug-rich core. Investigations of a series of drugs with different molecular architectures showed that the drug release rate was determined mainly by the stability of the drug aggregates in the core and the diffusive mass transport of drug molecules through the shell. Detailed studies of polyacrylate microgels interacting with amitriptyline hydrochloride showed that swelling of the shell network greatly influenced the release rate. Furthermore, experiments with a specially constructed microscopy cell was used to establish that the collapsed and swollen phases could coexist in equilibrium, and that the swelling of the network in the swollen phase depended on the proportion between them when present in the same microgel. The latter effect was related to the elastic coupling between the phases. Confocal Raman microscopy was employed to demonstrate, for the first time, the related elastic effect, that the concentration of amitriptyline in the swollen phase decreased with increasing proportion of the collapsed phase. Small-angle X-ray scattering showed that the collapsed phase had a disordered microstructure of drug micelles with ellipsoidal shape. The aggregation number increased with increasing concentration of drug in the microgel, most likely by incorporating the uncharged base form. By providing detailed information about thermodynamic properties and microstructures, the results of the thesis provide a basis for rational design of microgel drug delivery systems.

  • Techniques for the increased utilization of dose response variability in proton therapy Author: Erik Almhagen Link: Publication date: 2022-05-17 12:08

    Particle therapy is a form of radiation therapy in which protons and heavier ions are used, as opposed to photons in conventional radiation therapy. The biological effectiveness of particles compared to photons is often quantified as relative biological effectiveness (RBE). In clinical practice, protons are assumed to be 10% more efficient than photons, despite the fact that RBE is known to vary. On the other hand, variable RBE models can be used to describe the RBE at a given position as a function of a few parameters, such as the linear energy transfer (LET) of the beam. Questions of accuracy and validation have prevented the clinical introduction of variable RBE models. In this thesis, we tried to develop a variable RBE model for protons and carbon ions, and then apply it in a proton planning study.

    We started with developing a beam model for protons. It was based on measured data at the Skandion Clinic in Uppsala, Sweden. It is capable of describing the spatial, angular and energy distributions of a proton beam at a certain position in a treatment room. This, coupled with a particle transport engine, allows for accurate study of the physical properties of a clinical beam.

    Prior to developing our RBE model, we studied a number of publications containing proton in vitro cell survival data. It was found that the particle beams used included heavy secondary particle contamination and thus this need not be accounted for separately in a proton RBE model based on this data. Taking this into account, the subsequent RBE model did not provided increased accuracy compared to the considered proton RBE models. For carbon ions, accuracy was increased. Coupled with a treatment planning system, treatment plans taking into account RBE variability can thus be made with this RBE model.

    Finally, we applied the nanoCluE RBE model in a proton dose painting planning study, where the tumor target is given a heterogeneous dose based on an estimated radio sensitivity map of the tumor such that more resistant areas are given higher doses. Variable RBE was not beneficial in increasing the control probability of the tumor, but it did help in decreasing doses to nearby, healthy tissue.