| 21. |
- Abdelgadir, Moawia, 1965-
(författare)
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Clinical and Biochemical Features of Adult Diabetes Mellitus in Sudan
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The high prevalence of diabetes mellitus among the Sudanese population is linked to obesity, poor glycaemic control and a high rate of complications. This study investigated 1/ Leptin hormone and its correlations with different biochemical characteristics in Sudanese diabetic subjects, 2/ The impact of glycaemic control on pregnancy outcome in pregnancies with diabetes, 3/ The glycaemic response to Sudanese traditional carbohydrate foods, 4/ The influence of glucose self-monitoring on the glycaemic control among this population, 5/ The health related quality of life in Sudanese subjects with diabetes-related lower limb amputation. Leptin was significantly lower in diabetic subjects compared with controls of same BMI in both females (P =0.0001) and males (P =0.019). In diabetic subjects, serum leptin correlated positively with the homeostatic assessment (HOMA) of both beta-cell function (P =0.018) and insulin resistance (P =.038). In controls, leptin correlated only with insulin resistance. Pregnancy complications were higher among diabetic compared with control women (P<0.0001) and varied with the type of diabetes. Infants of diabetic mothers had a higher incidence of neonatal complications than those of non-diabetic women (P<0.0001). In six Sudanese traditional carbohydrate meals over all differences in incremental AUCs were significant for both plasma glucose (P = 0.0092) and insulin (P = 0.0001). Millet porridge and wheat pancakes displayed significantly lower post-prandial glucose and insulin responses, whereas maize porridge induced a higher post-prandial glucose and insulin response. In type 2 diabetic subjects SMBG or SMUG was not related to glycaemic control. In type 1 diabetic subjects, SMBG was significantly associated with better glycaemic control, as assessed by HbA1c (P=0.02) and blood glucose at clinic visits (P=<0.0001), similar associations were found for SMUG respectively. Neither glycaemic control nor glucose self-monitoring was associated with education level. Diabetic subjects with LLA had significantly poorer HRQL compared to a reference diabetic group (P=<0.0001). Duration of diabetes and amputation had negative impact on HRQL in subjects with LLA (P=<0.0001) respectively. Diabetic subjects with LLA had decreased sense of coherence and high presence of symptoms. Improving health services at the primary level is important to reduce the complications and burden of disease in the Sudanese population.
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| 22. |
- Abdsaleh, Shahin, 1957-
(författare)
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Core Biopsy of Breast and Axillary Lesions : Technical and Clinical Aspects
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aims of this work were to image and analyze the needle behavior at automated core biopsy, to investigate the clinical utility of an alternative core biopsy technique using a semiautomated gun in breast and axillary lesions, and also to compare core biopsy with surgical specimens in malignant breast lesions regarding histologic features and hormone receptor expression.In two experimental studies, using butter and silicon phantoms, respectively, the needle pass was imaged and its dynamic behavior studied. It was shown that the needle took a curved course in phantoms. It deviated to the same side as where the tip lay, and the degree of the curvature increased with increasing hardness of the phantoms. Our experimental methods can be applied for imaging of needle behavior and thereby improvement of needle configuration.In two clinical studies, a semiautomated gun was used for large needle core biopsy of breast and axillary lesions in two series of 145 and 21 patients, respectively. The sensitivity of the method for diagnosis of malignancy was 87% (108/124), and in 37% (31/83) of cases the full length of the needle notch was filled with specimen. No injury to the neurovascular structures of the axillary area was observed. It was concluded that the semiautomated gun can be used as an alternative to the automated gun when the size and location of the lesion render use of the automatic device uncertain or dangerous, e.g., in small breast lesions or lesions located in the axilla.In a series of 129 cases of breast cancer, comparison of core biopsy and surgical specimens showed that core biopsy provided enough information on the histologic type and grade of the lesions. Also, there was moderate to high concordance between the two methods for assessment of progesterone receptors and estrogen receptors (Spearman`s kappa 0.67 and 0.89, respectively).
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| 23. |
- Abdu, Yassir Ahmed Mohamed, 1966-
(författare)
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Mössbauer Spectroscopy of Meteoritic and Synthetic Fe-Ni Alloys
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis reports on the results of investigating Fe-containing minerals in meteorites, with focus on Fe-Ni minerals and their magnetic properties, along with some synthetic Fe-Ni analogues. The New Halfa meteorite, which fell in Sudan 1994, has been studied using Mössbauer spectroscopy, X-ray diffraction, and electron microprobe analysis techniques, and classified as an ordinary L-type chondrite of petrologic type 4. Mössbauer spectra of taenite-enriched samples from the metal particles of the New Halfa (L4) and Al Kidirate (H6) meteorites identify the following γ (fcc) Fe-Ni phases: the ferromagnetic atomically ordered taenite (tetrataenite) with ~ 50 at % Ni, the ferromagnetic disordered taenite with ~ 50 at % Ni, the low-Ni (~ 25 at %) paramagnetic taenite (antitaenite). The presence of the superstructure of tetrataenite is confirmed by synchrotron X-ray diffraction.Fe-rich γ (fcc) Fe-Ni alloys with compositions Fe79Ni21, Fe76Ni24, and Fe73Ni27, which serve as synthetic analogues of antitaenite, are prepared by mechanical alloying and subsequent annealing at 650 °C. The Mössbauer results indicate that these alloys are inhomogeneous and contain a high moment (HM) ferromagnetic Ni-rich phase (> 30 at % Ni) and a low moment (LM) paramagnetic Fe-rich phase, which orders antiferromagnetically at low temperature. The coexistence of these phases is attributed to phase segregation occurring on short range, probably nanometer scale, consistent with the Fe-Ni phase diagram below 400 °C where there is a miscibility gap associated with a spinodal decomposition in alloys with < 50 at % Ni.The combined high field Mössbauer spectroscopy and SQUID magnetometry results on these alloys at room temperature indicate large induced local magnetic moments in the paramagnetic part of the sample, which increases with increasing the Ni content. The results, when compared with the high field Mössbauer results on antitaenite from the metal particle of Al Kidirate and New Halfa meteorites may be used to estimate the Ni content of antitaenite in meteorites.High pressure 57Fe Mössbauer spectroscopy measurements up to ~ 41 GPa have been carried out at room temperature using the diamond anvil cell (DAC) technique in order to investigate the magnetic properties of γ (fcc) 57Fe53Ni47 alloy. The results indicate a pressure induced Invar effect at ~ 7 GPa and a non-magnetic or paramagnetic state above 20 GPa, demonstrating the volume dependence of the magnetic moment of γ (fcc) Fe-Ni alloys.
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| 24. |
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| 25. |
- Abdulla, Maysaa
(författare)
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Prognostic signficance of tumor cell markers in diffuse large B-cell lymphoma with special emphasis on lymphoma localization
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Diffuse large B-cell lymphoma (DLBCL) is the most common type of high-grade B-cell lymphoma with different clinical, morphological, immunophenotypical, and molecular features. DLBCL is curable in 60-70% of patients when treated with standard immunochemotherapy R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone).The main aim of this thesis is to identify prognostic factors in DLBCL by studying tumor markers (paper I and II), site of disease (paper III) and tumor microenvironment markers in primary DLBCL of the CNS (PCNSL) (paper IV) in order to better identify different risk groups of DLBCL patients.In papers I-III, we studied DLBCL patients treated homogeneously with R-CHOP. The negative prognostic impact of double protein expression of MYC and BCL2 so called “double-expressor lymphoma” (DEL) was a common finding in the three papers. In paper I, we detected DEL in 27% of patients, distributed with no significant difference between the germinal center derived B-cell subgroup (GCB) in 52% of cases and the non-GCB subgroup in 37% of cases. There was no significant difference in survival between GCB and non-GCB patients. The diagnosis in most of the patients with DEL was made on core needle biopsy in this paper. This finding was more thoroughly investigated in paper III with attention paid to the site of biopsy. In paper II, we evaluated the concordance of cell of origin (COO) assignment between gene expression profile (GEP) and immunohistochemistry (IHC) to identify the best predictor of survival in a DLBCL cohort including patients from Sweden and Denmark. The overall concordance between the two methods was 83%. We found that ABC/non-GCB subtype identified by both GEP and IHC is associated with the worst outcome. This finding indicates the importance of precise risk stratification in the era of precision medicine. DEL was more common in ABC patients categorized by GEP. In paper III, we identified abdominal lymph node involvement by radiological examination in 63% of DLBCL patients with an inferior survival, adverse clinical characteristics and significantly more frequent DEL. These findings may indicate a distinct biological behavior in patients with abdominal nodal disease. In paper IV, we demonstrated a significant association between IDO1 and PD-L1 in PCNSL patients. This finding indicates the crucial immunosuppressive role of these two molecules. In addition, in PCNSL low frequencies of MYC and BCL2 translocations and high frequency of BCL6 translocation was observed and DEL was detected in 49% of cases. Contrary to our results in systemic DLBCL in papers I-III, there was no significant prognostic impact of DEL in PCNSL.
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| 26. |
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| 27. |
- Abdurakhmanov, Eldar, 1977-
(författare)
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Discovery and evaluation of direct acting antivirals against hepatitis C virus
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Until recently, the standard therapy for hepatitis C treatment has been interferon and ribavirin. Such treatment has only 50% efficacy and is not well tolerated. The emergence of new drugs has increased the treatment efficacy to 90%. Despite such an achievement, the success is limited since the virus mutates rapidly, causing the emergence of drug resistant forms. In addition, most new drugs were developed to treat genotype 1 infections. Thus, development of new potent antivirals is needed and drug discovery against hepatitis C is continued.In this thesis, a FRET-based protease assay was used to evaluate new pyrazinone based NS3 protease inhibitors that are structurally different to the newly approved and currently developing drugs. Several compounds in this series showed good potencies in the nanomolar range against NS3 proteases from genotype 1, 3, and the drug resistance variant R155K. We assume that these compounds can be further developed into drug candidates that possess activity against above mentioned enzyme variants.By using SPR technology, we analyzed interaction mechanisms and characteristics of allosteric inhibitors targeting NS5B polymerases from genotypes 1 and 3. The compounds exhibited different binding mechanisms and displayed a low affinity against NS5B from genotype 3.In order to evaluate the activity and inhibitors of the NS5B polymerase, we established an SPR based assay, which enables the monitoring of polymerization and its inhibition in real time. This assay can readily be implemented for the discovery of inhibitors targeting HCV.An SPR based fragment screening approach has also been established. A screen of a fragment library has been performed in order to identify novel scaffolds that can be used as a starting point for development of new allosteric inhibitors against NS5B polymerase. Selected fragments will be further elaborated to generate a new potent allosteric drug candidate.Alternative approaches have successfully been developed and implemented to the discovery of potential lead compounds targeting two important HCV drug targets.
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| 28. |
- Abeid, Muzdalifat, 1973-
(författare)
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Improving Health-seeking Behavior and Care among Sexual Violence Survivors in Rural Tanzania
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this thesis was to assess the effects of providing community education and training to healthcare workers to improve community response, healthcare and support for rape survivors in the Kilombero district of Tanzania. The overall design of the project was to begin with an exploratory study (Paper I) to establish the community’s perceptions towards sexual violence and their perceived recommendations to address this issue. Using a structured questionnaire, the community’s knowledge and attitudes towards sexual violence were determined along with their associations with demographic factors (Paper II). Papers III and IV assessed the effect of healthcare workers’ training and a community information package, respectively, using a controlled quasi-experimental design. The findings highlighted the social norms and variety of barriers that impacted negatively on the survivors’ care-seeking from support services and health outcomes. Increasing age and higher education were associated with better knowledge and less accepting attitudes towards sexual violence. Training on the management of sexual violence was effective in improving healthcare workers’ knowledge and practice but not attitude. Knowledge on sexual violence among the communities in the intervention and comparison areas increased significantly over the study period; from 57.3% to 80.6% in the intervention area and from 55.5% to 71.9% in the comparison area. In the intervention area, women had significantly less knowledge than men at baseline (53% Vs 64%, p<.001).There was a reduction, though not significantly, in acceptance attitudes from 28.1% to 21.8% in favor of women. In conclusion, the current intervention provides evidence that healthcare workers’ training and community education is effective in improving knowledge but not attitudes towards sexual violence. The findings have potential implications for interventions aimed at preventing and responding to violence. The broader societal norms that hinder rape disclosure need to be re-addressed.
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| 29. |
- Abelson, Anna-Karin, 1978-
(författare)
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Genetic Risk Factors for Systemic Lupus Erythematosus : From Candidate Genes to Functional Variants
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this thesis has been to identify genetic variants that increase the susceptibility for Systemic Lupus Erythematosus (SLE), an autoimmune disease caused by a complex interplay between various genetic and environmental factors. Five different candidate genes were selected through different strategies, and were analysed for association with SLE in an attempt to distinguish some of the underlying mechanisms of this disease. Two of these genes, PD-L1 and PD-L2, appeared not to contain any major risk factors for SLE in the analysed European and Latin American populations. In two other genes, CD24 and STAT4, there appeared to be population-specific effects. The A57V amino acid substitution in the CD24 gene, previously implicated with multiple sclerosis, was associated in a Spanish cohort, with a weak trend in German samples, and no association in Swedish. The previously reported and highly convincing association of the STAT4 transcription factor gene was confirmed in all our cohorts. Interestingly, the results indicate the presence of at least two independent risk variants: the first, represented by a previously reported SNP, was the strongest in individuals of Northern European ancestry, and the second was more pronounced in individuals from Southern Europe and Latin America. We also report the identification of a novel susceptibility gene. The BANK1 gene, encoding a scaffold protein involved in B-cell activation, contains functional variants affecting important domains, which are associated in all investigated cohorts from Europe and Latin America. These results confirm the existence of replicable associations between genetic variants and SLE, which are common and present in many populations. The results also illustrate a certain degree of heterogeneity, where some risk factors could have variable effect in different populations.
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| 30. |
- Abelson, Klas, 1976-
(författare)
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Acetylcholine in Spinal Pain Modulation : An in vivo Study in the Rat
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The spinal cord is an important component in the processing and modulation of painful stimuli. Nerve signals from the periphery are relayed and further conducted to the brain (nociception) in the spinal cord, and the most essential modulation of painful information (antinociception) occurs here. Several neurotransmitters are involved in spinal pain modulation, among them acetylcholine. However, the role of acetylcholine has previously been little investigated. In the present thesis, the acetylcholine release in the spinal cord was studied in vivo. By using spinal microdialysis on anaesthetised rats, the effects on the intraspinal acetylcholine release of various receptor ligands and analgesic agents were examined. This, together with pain behavioural tests and in vitro pharmacological assays, was used to evaluate the role of acetylcholine in spinal pain modulation. The four studies in this thesis resulted in the following conclusions: An increased release of spinal acetylcholine is associated with an elevated pain threshold, while a decreased acetylcholine release is associated with hyperalgesia, as seen after systemic treatment with a muscarinic agonist and an antagonist. Lidocaine is a potent analgesic when given systemically. It was found to produce an increase of intraspinal acetylcholine after intravenous injection of analgesic doses. This effect was attenuated after muscarinic, and abolished after nicotinic, receptor blockade. Various a2-adrenergic ligands, associated with nociceptive or antinociceptive effects, were found to affect intraspinal acetylcholine release via action on nicotinic receptors. Finally, the involvement of spinal acetylcholine in the analgesic effects of aspirin and paracetamol was examined. It was found that spinal acetylcholine could participate in the analgesic effects of aspirin, but not of paracetamol. The present thesis provides data that clearly demonstrate a relationship between intraspinal acetylcholine and antinociception, and elucidate interactions between acetylcholine and other mechanisms that mediate antinociception in the spinal cord.
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