| 11. |
- Abdulkarim, Khadija
(författare)
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Population-Based Long-Term Follow-up of Patients with Myeloproliferative Neoplasms, complications and prognosis
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- ABSTRACT Philadelphia chromosome negative myeloproliferative neoplasms (Ph-MPNs) are rare clonal hematological malignancies, mainly including polycythemia vera (PV), essential thrombocythemia (ET) and myelofibrosis (MF). Patients with these diseases run a high risk of vascular complications and may transform to acute myeloid leukemia (AML). Population-based studies relating to these issues are few in number. The aims were (i) to investigate the rate of AML development in subtypes of Ph-MPNs, (ii) to determine whether clinical and bone marrow findings at diagnosis have an impact on survival and vascular complications in PV and ET, (iii) to find prognostic tools based on clinical findings in newly diagnosed PV and (iv) to describe the “real”-life data from newly diagnosed PV and ET. We have investigated these issues in population-based material; study (i) and (iii) were based on patients from both Gothenburg, Sweden, and the Côte d`Or area, France. Study (ii) was based only from Gothenburg and study (iv) comprised PV and ET patients in the National MPN Registry. In the median observation period of 15 years, 7% (56 of 795) of patients with Ph-MPN transformed to AML. The yearly rate of AML transformation was significantly higher in MF (1.09%) compared with that of ET (0.37%) and PV (0.38%); (p = 0.02 and p = 0.002 respectively). Patients with PV had a significantly shorter survival compared with the general Swedish population (HR 1.66; CI: (1.38-1.99); p < 0.001). For ET, however, the corresponding survival differences did not reach statistical significance (HR 1.23; CI: (0.97-1.51); p = 0.089). Low hemoglobin at the time of diagnosis predicted poor survival in ET (p = 0.0281) and splenomegaly predicted poor survival in PV (p = 0.037). Using multivariate analysis, independent risk factors at diagnosis for survival in PV patients were identified as age > 70 years, WBC > 13×109/L and thrombotic events. Patients with none of these risk factors had a 10-year relative survival (RS) of 84%, compared with 59% and 26% in patients with one and two or three risk factors respectively. In the fourth study, we showed that vascular complications preceded an MPN diagnosis in 35% of ET and 37% of PV and multivariate analysis identified low hemoglobin as a risk factor for thromboembolic complications in PV (p = 0.012), while in ET age > 65 years, WBC > 12 × 109 /L and the presence of the JAK2 V617F mutation were independent risk factors (p = 0.0004, p = 0.0038 and p = 0.0016 respectively).
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| 12. |
- Abdulle, Sahra, 1970
(författare)
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HIV-1 infection of the central nervous system. Markers of pathogenesis and antiretroviral treatment effects
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Human immunodeficiency virus type 1 (HIV-1) invades the central nervous system (CNS) early in the course of infection and either directly or through opportunistic infections causes a spectrum of neurological complications. The most severe manifestation of HIV-1 CNS infection is AIDS Dementia Complex (ADC), which occurs in approximately 20% of untreated patients with AIDS. ADC is considered the result of a complex interplay between immune activation effects and viral replication in the brain, which ultimately leads to neuronal injury and death. Reliable markers to diagnose HIV-1 associated CNS injury, track disease progression, and identify patients at risk of developing ADC are lacking. Such markers would also be beneficial in evaluating the efficacy of antiretroviral treatment (ART) in the CNS, as well as to provide insights into the pathogenesis of HIV-1 CNS infection.HIV-1 elicits intrathecal cell-mediated and humoral immune activation. We found that ART effectively decreased the cerebrospinal fluid (CSF) concentrations of neopterin and beta2-microglobulin, but had little effect on the elevated IgG index. However, almost half of the patients still had slightly elevated levels of neopterin after 2 years of follow-up. Phylogenetic analyses have identified 3 distinct HIV-1 genetic groups. Group M, which is responsible for most of the global HIV-1 epidemic is further subdivided into subtypes and circulating recombinant forms (CRFs). Most of the current knowledge of HIV-1 CNS infection is based on studies of subtype B, which is predominant in the western world. However, subtypes other than subtype B are responsible for most of the epidemic outside the western world, and HIV-1 infections due to subtypes other than B are rapidly increasing across Europe. Markers of HIV-1 CNS infection such as HIV-1 RNA, neopterin, and white blood cell (WBC) count in CSF were measured and compared in patients infected with different HIV-1 subtypes. We did not find any significant subtype-specific differences in the neuromarkers evaluated in this study. Thus, subtypes do not appear to influence neuropathogenesis.Although there is no evidence of productive infection of neurons the end-result of HIV-1 CNS infection is neuronal damage and loss. We investigated the potential of CSF neurofilament (NFL), a sensitive indicator of axonal injury, as a marker of HIV-1 associated neurodegeneration. CSF NFL concentrations were higher in patients with ADC than in neuroasymptomatic patients, or patients with primary HIV-1 infection. Patients with severe ADC had higher CSF NFL levels compared to those with milder disease. CSF NFL declined with ART to the limit of detection in parallel with virological response and neurological improvement in patients suffering from ADC.Neurocognitive impairment remains a major concern in HIV-1 infection despite the success of ART. Studies on the pathogenesis, epidemiology, and the effects of ART on HIV-1 CNS infection are important to improve patient management.
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| 13. |
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| 14. |
- Abel, Frida, 1974
(författare)
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Genetic studies of neuroblastoma with emphasis on the apoptotic pathway
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Aim: The objective of this thesis was to find genes and chromosomal regions involved in neuroblastoma (NB) tumor progression. NB is a childhood tumor of the sympathetic nervous system that generally occurs spontaneously. Biologically, NB has a complex heterogeneity from tumor progression to tumor regression, dependent on clinical stage and age at diagnosis. The main genetic markers, which are also of prognostic value in NB, are amplification of the oncogene MYCN, deletion of chromosome arm 1p and gain of chromosome arm 17q. Results: We have been shown using fluorescence in situ hybridization (FISH) on a Scandinavian tumor material, that 17q gain is present in approximately 65% of all NB stages, is significantly associated with poor prognosis and predicts survival. The gene encoding somatostatin receptor 2 (SSTR2), localized in chromosome region 17q24, was not found to be mutated in any NB, when analyzed with PCR-based single stranded conformation polymorphism/heteroduplex (SSCP/HD) and DNA sequencing. In a tentative effort of defining of the location of a general embryonal tumor suppressor gene (TSG) on 1p, we combined the smallest region of overlap (SRO) of 1p deletions in NB tumors and germ cell tumors (GCTs). We thus delimited the NB/GCT SRO to approximately 5 cM between markers D1S508 and D1S244, and fine-mapped this region by radiation hybrid mapping and construction of a bacterial artificial chromosome (BAC) contig. A homozygously deleted region in an NB cell line was found to partially overlap the proximal part of the 5 cM-SRO defined by us, which further focused our search for a TSG to a 500 kb candidate region in 1p36.22. Two attractive candidate NB TSGs, DFFA and CASP9, are both located in 1p36.2 and encode key apoptotic mediators. In fact, DFFA resides in the 500 kb TSG candidate region. Via sequence analysis of the entire tumor material, we found three different coding alterations in DFFA which all affect the highly conserved N-terminal regulatory domain of DFF45. Using RT-PCR and real-time RT-PCR (TaqMan) studies, we were able to show that both DFFA and CASP9 are preferably expressed in NB tumors with favorable outcome. It has been proposed that lack of apoptosis plays an important role in tumor progression. We therefore screened an array with cDNAs involved in the apoptotic process, to find genes differentially expressed in NB tumors with unfavorable versus favorable biology. Using real-time RT-PCR analysis, we verified the differential expression of several transcripts encoding mitochondrial apoptotic mediators. Conclusions: We have shown that 17q gain is the most frequently detected alteration in NB and that it is associated with established prognostic factors. We narrowed down the TSG candidate region on 1p and found mutations in a gene localized in the region possessing fundamental functions in apoptosis. Our results also suggest that the mitochondrial apoptotic pathway is suppressed at multiple steps in advanced stages of NB tumors, due to imbalance between anti-apoptotic and pro-apoptotic mediators.
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| 15. |
- Abelin, Åsa, 1953
(författare)
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Studies in Sound Symbolism
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis investigates how the Swedish lexicon is structured with respect to sound symbolism, the productivity of phonesthemes and cross language similarities in certain areas of sound symbolism. The Swedish lexicon has been analyzed with emphasis on the sound symbolic properties of initial and final consonant clusters, and to a certain extent of vowels. Approximately 1, 000 lexemes were judged to be sound symbolic and the outcome of the analysis are tentative phonesthemes, i.e. motivated connections between meanings and consonant clusters. Almost all Swedish initial consonant clusters and many of the final consonant clusters may carry sound symbolic meanings. Lexically infrequent clusters are utilized to a larger extent than lexically frequent clusters. No two consonant clusters have exactly the same semantic profile. Phonesthemes have different sound symbolic strength, i.e. some are clearly sound symbolic (i.e. a high percentage of the words beginning with a certain cluster are sound symbolic), and carry either one meaning or several meanings. Other (candidates for) phonesthemes are weaker and not so clearly sound symbolic. The meanings of most phonesthemes are relatable to the senses: hearing, vision or tactile sensation, or they are metaphorically or metonymically connected to the senses. The most common semantic features occurring are often related to synaesthesia. The productivity of phonesthemes was tested in experiments of production and understanding. The experiments show that in interpretation no constructed word is interpreted as expected by all subjects, but that all of the constructed words are interpreted correctly by some subjects. The most common semantic features found in the lexical analysis are also often the most successfully interpreted by subjects. For production, the experiments indicate that subjects tend to encode the semantic features in initial clusters rather than in final clusters. Final consonant clusters seem to be of less importance than the initial clusters in new sound symbolic words in Swedish. For the contrastive studies, the general results are that there are both similarities and differences between the expressions in the different languages. The variation is greater for some semantic fields than for others.
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| 16. |
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| 17. |
- Abelsson, Tobias
(författare)
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Primärvården och evidensen Evidensbaserad praktik i svensk offentlig primärvård från olika perspektiv
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The development of information technology and growing insight into the limitations of the old paradigm of practicing medicine resulted in historical events that led to the emergence of evidence-based practice (EBP). Which centers upon putting the evidence of science and clinical knowledge of the health professional in dialogue with the patient and his or her needs and preferences in receiving care. The thesis aim to investigate the prerequisites of evidence-based practice following the evidence-based medicine (EBM) model. Which was accomplished by conducting four studies spread across the domains of evidence-based practice. The studies combined qualitative and quantitative methodology and results in a contemporary description of the attitudes towards evidence-based practice and its possibility to be applied within the primary healthcare organization of today. The key findings of the thesis show that increasing demand for efficiency results in a chronic lack of time and resources to properly execute individual notions of what evidence-based practices ought to be. The deficiency of knowledge and resources is present on both co-worker and managerial levels. In addition, the results indicate that there exist attitudes towards research are somewhat reluctant, that is, that research and evidence-based practice are recognized as something positive and needed. Although research and tasks associated with evidence-based practice seemed somewhat extracurricular. At the same time, it´s mentioned that co-workers also stated that it was sometimes hard to get information relevant for use in primary care. The perceived barrier signals that the influence of economic value and efficiency takes precedence on a practice that ought to be aimed at helping the patient. Primary healthcare is very much heavily reliant on information, which in turn is dependent of internal and external factors to direct resources such as time. Today, there is a growing patient-centered care. Aimed at reducing the existent gap between evidence and clinical practice.
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| 18. |
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| 19. |
- Abou-Ali, Hala, 1972
(författare)
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Water and Health in Egypt: An Empirical Analysis
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis is an empirical work dealing with water issues in Egypt where the emphasis is put on the analysis of the relationship: inadequate water quality and health impacts. The first chapter includes a general discussion of water resources in Egypt and other developing countries. This chapter briefly also deals with water tariffs and sustainable water pricing in Cairo. In the second chapter the impacts of water and sanitation on child mortality in Egypt are assessed. The analysis is conducted using a three-part model specification, comprising discrete choice to model the child prospects of dying during the neonatal period. The remaining parts use transition models, in which unobserved heterogeneity is accounted for, to model infant and childhood risk of death. The results show that access to municipal water decreases the risk, and sanitation is found to have a more pronounced impact on mortality than water. The results suggest that increasing the awareness of the Egyptian population relative to health care and hygiene is an important means to decrease the risk of child mortality. Moreover, gender discrimination is found to have an important effect beyond the neonatal period. In the third chapter, controlling for the Egyptian households' choice of health infrastructure (i.e., sanitation facility and water accessibility) is done by means of a discrete choice approach consistent with the random utility model. Evidence of the importance of the indirect effect of the source of drinking water on neonatal mortality is found, but generally the indirect effect is negligible. Furthermore, changes in wealth and educational levels are assessed taking into consideration a priori the choice of health infrastructure. The analysis suggests that wealth and education contribute loosely to the child mortality reduction. The fourth chapter analyzes the impact of better water quality on health improvements using two stated preference methods: choice experiments and the contingent valuation method. These methods were administered to a random sample of 1500 households in metropolitan Cairo, Egypt. The results show that both methods give quite the same welfare measures. Moreover, households in metropolitan Cairo do have a positive willingness to pay for reducing health risks owing to water quality that amounts to roughly double their current water bills. This finding suggests that the willingness to pay is rather small compared to the likely cost.
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| 20. |
- Abraham, Getahun Yacob
(författare)
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Education for Democracy? : Life Orientation: Lessons on Leadeship Qualities and Voting in South African Comprehensive Schools
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This study takes as its starting point how teachers understand, interpret and teach social development aspects of Life Orientation in South African comprehensive schools. The specific focus is on lessons on leadership qualities and voting for third grade learners in four schools, each dominated by either Black, Coloured, White or mixed groups of learners. Field work with an ethnographic approach and a qualitative strategy was used to gain access to empirical data. Policy and curriculum documents, guidelines and textbooks were used. Classroom observations in four classes and interviews with 14 third grade teachers were conducted. Theoretical concepts of construction, deconstruction and reconstruction are applied. Ulf P Lundgren’s Frame Factor Theory is used to study school organization. Basil Bernstein’s Pedagogical Devices are considered when examining the different levels of pedagogical activities. To be a teacher in South Africa one needs to attend at least two years of teacher education after completing high school. Teachers in the classes studied underwent their teacher education during apartheid years. Due to limited in-service training, they sometimes experience problems of understanding and interpreting the learning area, which they usually tackle by consulting documents, colleagues or school authorities. The learners’ understanding varied based on their family background and type of school they attended. There were enormous differences in material, financial and organisational resources between classes and schools. The resources for teaching leadership qualities and voting were not, however, different between the classes. The lessons were teacher dominated and direct transmission was used as a method. The way teachers facilitated the lesson on leadership qualities and voting varied but all showed some democratic shortcomings. Apart from answering questions, learners were neither invited nor encouraged to participate to further their understanding of the theme. Limited aspects of leadership qualities were discussed, individual leaders’ roles were emphasised and the teachers picked candidates for class leaders in three of the classes. It was also evident that the class environments were not suitable for critical or creative thinking and democratic upbringing. The schools reproduced norms, values, languages and cultures of the different groups. Officially, teachers emphasised the common national South African identity. This emphasis on national identity could disguise the injustice some groups experience in society.
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