Thesis (doctoral)--Ludwig-Maximilians-Universität, 1996.

Thesis (doctoral)--Ludwig-Maximilians-Universität, 1996.

Thesis (M.N.)--Memorial University of Newfoundland, 1996. / Typescript. Bibliography: leaves 94-104. Also available online.

Thesis (Ph. D.)--Université Laval, 2005. / Title from PDF title page (viewed on Oct. 5, 2006). Includes bibliographical references (p. [299]-320).

Philosophiae Doctor - PhD / The continued success of antiretroviral programmes in the treatment of HIV is dependent on access to a cost-effective HIV drug resistance test (HIV-DRT). HIVDRT involves sequencing a fragment of the HIV genome and characterising the presence/absence of mutations that confer resistance to one or more drugs. HIV-DRT using conventional DNA sequencing is prohibitively expensive (~US$150 per patient) for routine use in resource-limited settings such as many African countries. While the advent of ultra deep pyrosequencing (UDPS) approaches have considerably reduced (3-5 fold reduction) the cost of generating the sequence data, there has been an even more significant increase in the volume of data generated and the complexity involved in its analysis. In order to address this issue we have developed Seq2Res, a computational pipeline for HIV drug resistance test from UDPS genotypic data. We have developed QTrim, software that undertakes high throughput quality trimming of UDPS sequencing data to ensure that subsequently analyzed data is of high quality. The comparison of QTrim to other widely used tools showed that it is equivalent to the next best method at trimming good quality data but outperforms all methods at trimming poor quality data. Further, we have developed, and evaluated, a computational approach for the analysis of UDPS sequence data generated using the novel Primer ID that enables the generation of a consensus sequence from all sequence reads originating from the same viral template, thus reducing the presence of PCR and sequencing induced errors in the dataset as well as reducing. We see that while the Primer ID approach does undoubtedly reduce the prevalence of PCR and sequencing induced errors, it artificially reduces the diversity of the subsequently analysed data due to the large volume of data that is discarded as a result of there being an insufficient number of sequences for consensus sequence generation. We validated the sensitivity of the Seq2Res pipeline using two real biological datasets from the Stanford HIV Database and five simulated datasets The Seq2Res results correlated fully with that of the Stanford database as well as identifying a drug resistance mutations (DRM) that had been incorrectly interpreted by the Stanford approach. Further, the analysis of the simulated datasets showed that Seq2Res is capable of accurately identifying DRMs at all prevalence levels down to at least 1% of the sequence data generated from a viral population. Finally, we applied Seq2Res to UDPS resistance data generated from as many as 641 individuals as part of the CIPRA-SA study to evaluate the effectiveness of UDPS HIV drug resistance genotyping in resource limited settings with a high burden of HIV infections. We find that, despite the FLX coverage being almost three times as much as that of the Junior platform, resistance genotyping results are directly comparable between both of the approaches at a range of prevalence levels to as low as 1%. Further, we find no significant difference between UDPS sequencing and the "gold standard" Sanger based approach, thus indicating that pooling as many as 48 patient's data and sequencing using the Roche/454 Junior platform is a viable approach for HIV drug resistance genotyping. Further, we explored the presence of resistant minor variants in individual's viral populations and find that the identification of minor resistant variants in individuals exposed to nevirapine through PMTCT correlates with the time since exposure. We conclude that HIV resistance genotyping is now a viable prospect for resource limited setting with a high burden of HIV infections and that UDPS approaches are at least as sensitive as the currently used Sanger-based sequencing approaches. Further, the development of Seq2Res has provided a sensitive, easy to use and scalable technology that facilitates the routine use of UDPS for HIV drug resistance genotyping.

Inledning: Vid en förvärvad hjärnskada är delaktighet i rehabiliteringen en central del för patientens återanpassning till vardagen och eventuellt tillbakabildande av förlorade funktioner. Delaktighet i vårdförloppet leder till en ökad teoretisk förståelse och praktisk insikt hos patienten. Syfte: Syftet med denna studie var att beskriva hur vuxna personer med förvärvad hjärnskada upplever/har upplevt delaktighet under sin vårdtid på en rehabiliteringsavdelning. Metod: Detta är en kvalitativ studie med beskrivande design med semistrukturerade intervjuer som datainsamlingsmetod. Tio patienter som vårdats minst fem arbetsdagar på en rehabiliteringsavdelning intervjuades gällande frågor om delaktighet under vårdtiden på rehabiliteringsavdelningen. En kvalitativ innehållsanalys inspirerad av Graneheim och Lundman (2012) användes för att analysera insamlad data på latentnivå. Resultat: Utifrån temat ”delaktighet” uppstod tre kategorier: kompetent personal, informerad patient, samt självständighet. Temat ”icke-delaktighet” resulterade i två kategorier: bristfällig information och kontrollförlust. Det var flera av informanternas berättelser som liknade varandra i fråga om delaktighet på vårdavdelningen. Samtliga informanter beskrev att de upplevt sig vara delaktiga någon gång under vårdtiden på rehabiliteringsavdelningen. Det handlade bland annat om att de upplevt att de fått tillräcklig information från personalen angående sjukdom och vårdförlopp, att det fanns kompetent personal som anpassade sig efter patienternas individuella behov och önskemål samt möjlighet till självständighet under exempelvis träning. Ett flertal informanter beskrev även upplevelser av att inte vara delaktiga under vårdtiden. Bristfällig information från personalens sida samt en känsla av kontrollförlust var de huvudsakliga anledningarna till detta. Slutsats: Denna studie kan bidra till en ökad förståelse hos vårdpersonal angående delaktighet under rehabiliteringstiden för patienter med förvärvad hjärnskada. Då vårdtiderna kan vara långa på rehabiliteringsavdelningen är det särskilt viktigt med en god kontakt och bra kommunikation med patienterna för delaktighet och en patientcentrerad vård.

BACKGROUND: Organelle retention is a form of mixotrophy that allows organisms to reap metabolic benefits similar to those of photoautotrophs through capture of algal prey and sequestration of their plastids. Mesodinium rubrum is an abundant and broadly distributed photosynthetic marine ciliate that steals organelles from cryptophyte algae, such as Geminigera cryophila. M. rubrum is unique from most other acquired phototrophs because it also steals a functional nucleus that facilitates genetic control of sequestered plastids and other organelles. We analyzed changes in G. cryophila nuclear gene expression and transcript abundance after its incorporation into the cellular architecture of M. rubrum as an initial step towards understanding this complex system. METHODS: We compared Illumina-generated transcriptomes of the cryptophyte Geminigera cryophila as a free-living cell and as a sequestered nucleus in M. rubrum to identify changes in protein abundance and gene expression. After KEGG annotation, proteins were clustered by functional categories, which were evaluated for over- or under-representation in the sequestered nucleus. Similarly, coding sequences were grouped by KEGG categories/ pathways, which were then evaluated for over- or under-expression via read count strategies. RESULTS: At the time of sampling, the global transcriptome of M. rubrum was dominated (~58-62 %) by transcription from its stolen nucleus. A comparison of transcriptomes from free-living G. cryophila cells to those of the sequestered nucleus revealed a decrease in gene expression and transcript abundance for most functional protein categories within the ciliate. However, genes coding for proteins involved in photosynthesis, oxidative stress reduction, and several other metabolic pathways revealed striking exceptions to this general decline. CONCLUSIONS: Major changes in G. cryophila transcript expression after sequestration by M. rubrum and the ciliate's success as a photoautotroph imply some level of control or gene regulation by the ciliate and at the very least reflect a degree of coordination between host and foreign organelles. Intriguingly, cryptophyte genes involved in protein transport are significantly under-expressed in M. rubrum, implicating a role for the ciliate's endomembrane system in targeting cryptophyte proteins to plastid complexes. Collectively, this initial portrait of an acquired transcriptome within a dynamic and ecologically successful ciliate highlights the remarkable cellular and metabolic chimerism of this system.

This thesis analyses the aims and objectives of the EU Acquired Rights Directive (ARD) in the context of the larger evolution of EU labour law itself. The thesis presents the overall goal of the ARD as that of striking an appropriate balance between the employer’s prerogative to transfer the business and the employee’s interest in not having the security of the job unduly threatened by such transfers. Given the current complexity and incoherence of the law regulating economic dismissals in the context of transfers, the central argument of the thesis is that there is a need for a clearer conceptual framework for defining and understanding the rights and obligations in the Acquired Rights Directive (ARD). It is suggested that the principles of legitimate expectations and proportionality are ideally adapted to play this role. In analyzing the teleology of the ARD based on these principles, this study not only assists in understanding and explaining the ARD itself, but also has wider implications for understanding the challenges facing European social policy in the field of employment protection. In its attempts to reconcile fundamental economic freedoms of employers on the one hand, and fundamental rights of employees on the other, the Court of Justice has frequently relied upon the proportionality principle to achieve a ‘fair balance’ between both parties. Following the interpretations of ‘proportionality’ in Viking and Laval, there is admittedly a fear that the proportionality balancing is likely to accord an almost absolute priority to the employers’ economic freedoms. The thesis is cognizant of this danger, and therefore advocates a ‘symmetrical’ approach to balancing. In this way the thesis offers some insight into the potential for the ARD to remain continuously effective in times of economic crisis. The study therefore finds reason to be optimistic about the prospects for the ARD and other standard-setting directives in the future of social Europe.

The overall aim of this thesis was to describe occupational therapy practice for clients with cognitive impairment following acquired brain injury (CIABI) from the perspective of practicing occupational therapists (OTs). To fulfill this aim, qualitative and quantitative approaches were used including interviews (Study I) and questionnaires (Studies II -IV). Based on the qualitative descriptions generated in Study I, a questionnaire was developed and evaluated for content validity and test-rest validity (Study II). The questionnaire was then used in a survey (Study III). The reactive Delphi technique was used to empirically define the aspects that OTs found to be consistent with the concept of therapeutic use of self (Study IV). The results showed that a predominant practice pattern was the use of ADL activities for intervention regardless of whether limitations in occupational performance or cognitive function were assessed, or whether the approach to therapy was remedial or compensatory. General ADL-instruments were used more than instruments focused on impairment level. Therapies covering a wide range of cognitive impairments, and abilities important to organizing and executing occupational performance were commonly targeted. Therapies targeting clients’ activity limitations were prioritized before remediating impairment. Therapeutic use of self was regarded as being important and the results identified clientspecific aims not earlier described in relation to therapeutic use of self. Another prominent practice pattern was the collaborative approach toward clients, relatives, and other staff. Theories used to support practice were primarily general. Occupational therapy practice for clients with CIABI was found to be complex, and the practice patterns were affected by circumstances such as the ‘hidden’ nature of the cognitive impairments, perceived lack of knowledge, and organizational issues. The results of this thesis can be used as a foundation for further research on practice patterns or the specific therapies used. It can facilitate discussions on strengths and weaknesses witcurrent practice, the need for development, and research utilization.

Non-suicidal self-injury (NSSI) is considered a strong predictor of suicidal behavior, although the exact relationship between NSSI and suicide is not clear. Several factors have been suggested in previous research, including attitudes toward one’s own body, thoughts and beliefs regarding death and suicide, and the ability to cause physical harm to oneself. In the current study, the researcher obtained data from 285 young adult participants who reported a history of NSSI. Two multiple mediation models were tested in which body protection, suicide-related concerns, and acquired capability for suicide were examined as mediators of the relationship between NSSI and suicide attempt frequency. The first model, in which the predictor was NSSI frequency, was not supported. The second model, in which the predictor was NSSI versatility of methods, was partially supported; the only significant mediator was suicide-related concerns. These results add to the literature regarding the relationship between NSSI and suicide.