| 1. |
- Johnsson, Inger W, 1973-
(author)
-
Long-term metabolic effects of a high birth weight
- 2019
-
Doctoral thesis (other academic/artistic)abstract
- The intrauterine environment influences foetal growth as well as future response to risk factors for disease. This occurs partly through epigenetic mechanisms. Thus, birth weight is a possible risk marker of adult disease. Low birth weight is a well-known risk factor for adult disease, particularly when associated with obesity and a U-shaped relationship between birth weight and several metabolic diseases has been suggested.In this thesis we investigated associations between a high birth weight and risk of adult disease, e.g. obesity, cardiovascular disease, type 2 diabetes and gestational diabetes.By analyses of national register data on 759 999 subjects up to the age of 37 years, we could demonstrate an increased risk of type 2 diabetes in males, but not in females, with a high birth weight (>2 SDS). The increase was particularly pronounced in males with a birth weight >3 SDS. There was an association between high birth weight and obesity in males and females, but no such relation was seen for hypertension or serum lipid abnormalities.In a clinical study, 27 cases with a birth weight ≥4 500 grams were compared with 27 controls with normal birth weight, regarding risk factors for cardiovascular disease and diabetes. The cases had a greater radial artery intima thickness and intima:media ratio compared with the controls indicating early atherosclerotic changes. Body mass index, body composition, insulin sensitivity, lipid profiles, blood pressure, resting energy expenditure and respiratory quotient did not differ between cases and controls, but females with a high birth weight had a more disadvantageous distribution of body fat.In order to investigate associations between birth weight and pregnancy outcomes, register data on 305 893 females was analysed. The results demonstrated an association between the female´s own birth weight and offspring birth weight. A high maternal birth weight was associated with increased risk of obesity. The risk of gestational diabetes was increased in females with a low, but not a high birth weight.In conclusion, subjects with a moderately high birth weight did not differ substantially from those with a normal birth weight regarding risk factors for cardiovascular disease. However, differences in arterial wall dimensions were demonstrated in a clinical investigation, and there were differences in BMI and risk of type 2 diabetes on a population level. Since risks are most pronounced in subjects with a birth weight >3 SDS, this group is in particular need of follow up and disease preventive measures.
|
|
| 2. |
- Zetterling, Maria, 1966-
(author)
-
Clinical Studies in the Acute Phase of Subarachnoid Haemorrhage
- 2010
-
Doctoral thesis (other academic/artistic)abstract
- Patients admitted in similar clinical condition after spontaneous SAH can develop very different clinical courses. This could depend on the severity of the initial global ischemic brain injury at ictus. In the present study, we explored relations between clinical and radiological parameters at admission that indicate a more severe initial impact, and the following days hormone levels and brain metabolism. Early global cerebral oedema (GCE) on computed tomography occurred in 57 % of SAH patients and was associated with a more severe clinical condition. The brain’s glucose metabolism, measured with intracerebral microdialysis (MD), changed the first days. MD-glucose was initially high and MD-pyruvate low. MD-glucose gradually decreased and MD-pyruvate and MD-lactate increased, suggesting a transition to a hyperglycolytic state. This was more pronounced in patients with GCE. Similar patterns were seen for interstitial non-transmitter amino acids. From initial low concentrations, they gradually increased in parallel with MD-pyruvate. The amino acid concentrations were higher for patients admitted in better clinical condition. Insulin lowered MD-glucose and MD-pyruvate even when plasma glucose values remained high. P-ACTH and S-cortisol were elevated early after SAH. GCE was associated with higher S-cortisol acutely. Urine cortisol excretion, indicating levels of free cortisol, were higher in patients in a better clinical condition. Suppressed P-ACTH occurred in periods of brain ischemia. We suggest that GCE on the first CT scan is a warning sign indicating increased vulnerability if the patient is exposed to compromised energy supply or increased energy demand. Reduction of blood glucose after SAH should be done with caution. The temporal change of the glucose metabolism and the amino acid concentrations probably reflect activated repair mechanisms. This should be considered in the intensive care treatment of SAH patients. Finally, our results support earlier observations that the response of the hypothalamic-pituitary-adrenal system is important in critical care.
|
|
| 3. |
- Conze, Tim, 1977-
(author)
-
Ligation-mediated Molecular Analysis of Influenza Subtypes, Splicing and Protein Glycosylation
- 2010
-
Doctoral thesis (other academic/artistic)abstract
- Binder-based assays are employed throughout the life sciences. Powerful signal amplification techniques have enabled detection of very rare molecule species diluted in simple buffers. Unspecific binding of primary binders leads to increased background in more complex samples. By requiring two recognition events, ligation-based molecular analyses provide highly specific detection of biomolecules in complex samples. We developed a highly multiplexed padlock-ligation assay targeting signature sequences in the hemagglutinin and neuraminidase genes. From a panel of 77 avian influenza isolates of all major serotypes, 97% were genotyped correctly in accordance with previous classifications by classical diagnostic methods (Paper I). Alternative splicing is an important mechanism expanding the proteome. Current analysis techniques fail to provide sequences of complete transcripts beyond the read length of sequencing instruments. We devised and implemented a strategy to compress the sequence information contained in the splicing pattern of a transcript into the presence or absence of sequence-blocks. We demonstrate that this assay yields information about the splicing patterns in thousands of transcripts from cellular cDNA (Paper II). Expression changes of mucin proteins and glycosylation structures are frequently observed from the early stages of cancer development. Expression of mucin 2 and sialyl-Tn are common features of intestinal metaplasia and gastric cancer, and are known to co-locate. Here we have developed an in situ proximity ligation assay (PLA) directed against mucin 2 and sialyl-Tn. Our study on intestinal metaplasia and gastric cancer tissue sections identified mucin 2 as a major carrier of sialyl-Tn in these conditions, and demonstrated how conveniently glycosylation of proteins can be studied by in situ PLA (Paper III). This thesis shows how the dual recognition requirement of ligation-based assays can be employed to detect target molecules with high specificity, to analyze several sequence features of nucleic acids or to study the proximity of two antigens in situ.
|
|
| 4. |
- Nilsson, Fritjof, Docent, 1978-, et al.
(author)
-
Nanocomposites and polyethylene blends: two potentially synergistic strategies for HVDC insulation materials with ultra-low electrical conductivity
- 2021
-
In: Composites Part B: Engineering. - : Elsevier BV. - 1359-8368 .- 1879-1069. ; 204
-
Journal article (peer-reviewed)abstract
- Among the various requirements that high voltage direct current (HVDC) insulation materials need to satisfy, sufficiently low electrical conductivity is one of the most important. The leading commercial HVDC insulation material is currently an exceptionally clean cross-linked low-density polyethylene (XLPE). Previous studies have reported that the DC-conductivity of low-density polyethylene (LDPE) can be markedly reduced either by including a fraction of high-density polyethylene (HDPE) or by adding a small amount of a well dispersed, semiconducting nanofiller such as Al2O3 coated with a silane. This study demonstrates that by combining these two strategies a synergistic effect can be achieved, resulting in an insulation material with an ultra-low electrical conductivity. The addition of both HDPE and C8–Al2O3 nanoparticles to LDPE resulted in ultra-insulating nanocomposites with a conductivity around 500 times lower than of the neat LDPE at an electric field of 32 kV/mm and 60–90 °C. The new nanocomposite is thus a promising material regarding the electrical conductivity and it can be further optimized since the polyethylene blend and the nanoparticles can be improved independently.
|
|
| 5. |
- Nilsson, Kenneth, Docent, 1953-, et al.
(author)
-
Impact of prolonged storage of clinical samples at 4 degrees C on the recovery of dermatophytes by culture or PCR analysis
- 2019
-
In: Journal de Mycologie Médicale. - : MASSON EDITEUR. - 1156-5233 .- 1773-0449. ; 29:1, s. 1-6
-
Journal article (peer-reviewed)abstract
- Dermatophytes are common pathogens in superficial mycoses that are routinely identified by culture or PCR analysis of freshly collected skin, nail or hair specimens. Although clinical samples are normally processed without delay, practical or research issues may necessitate sample storage until later analysis. However, the influence of extended sample storage on the ability to recover fungi by culture vs. PCR analysis has not been specifically studied. Here, a total of 172 dermatological samples collected from 2013-2015 were examined before and after refrigerated storage at 4 degrees C for 10.2-32.3 (mean 25.6) months. By culture, 35% of the dermatophyte-containing fresh samples remained positive at reexamination. At species level, only 19% of initially Trichophyton rubrum-positive samples yielded a positive result after refrigeration, whereas few samples containing Trichophyton violaceum, Microsporum canis or Microsporum audouinii remained culture-positive. Using PCR, 76% of dermatophyte DNA-positive fresh samples were still positive at re-analysis. Notably, 92% of the samples targeted by the T. rubrum DNA primer remained positive after storage. Hence, PCR analysis is more favourable than cultivation with regard to the detectability of dermatophytes in long-term refrigerated clinical samples.
|
|
| 6. |
- Nilsson, Ola, 1968-
(author)
-
Förtroendeperspektiv på aktiebolagsrevision
- 2016
-
Doctoral thesis (other academic/artistic)abstract
- This dissertation is motivated by the circumstance that theoretical discussions of statutory auditing are dominated by the principal-agent perspective. The effect of this has been so pervasive that general assumptions characterising the principal-agent perspective may have become regarded as true. On this basis, there are fears that important decisions, for example, could be made on erroneous grounds, as principal-agent perspectives essentially lack external validity. Critics have pointed out that the basic assumptions of the principalagent theoretical perspective – that individuals always act out of self-interest and that there is a constant risk of opportunism – become too general and need to be made more nuanced. It has been argued that trust, which may be regarded as a contrasting concept to self-interest and opportunism, might be integrated to support external validity. It may also be noted that this term – trust – has become a catchword for describing the significance and role of auditing in the practical discourse. These arguments support the relevance of this dissertation, where the overall purpose is to elaborate on a theoretical perspective on the statutory auditing including trust. This will contribute to explaining and understanding statutory auditing in a way that balances the currently dominant theoretical perspectives on auditing.The dissertation accomplishes this in three related ways building on three parts. The first of these aims to substantiate a theoretical proposition based on trust theory. It focuses on clarifying various dimensions of trust which may contribute to analysing the role and significance of auditing. The second is an empirical study aimed at elucidating auditing from a systems perspective and contains a historical analysis in which texts are used to reproduce and analyse some of the developments on the basis of the theoretical framework. The third is an empirical study which concerns auditing from an investors perspective. It is based on a survey of equity investors in companies listed on the Stockholm stock exchange, and also based on the theoretical framework. The two empirical studies contribute to substantiating the proposition that trust is a concept that should be integrated in theories explaining the role and function of auditing.
|
|
| 7. |
- Philipson, Ola, 1979-
(author)
-
Modeling Amyloid-β Pathology in Alzheimer’s Disease Using the Arctic Mutation
- 2010
-
Doctoral thesis (other academic/artistic)abstract
- The Arctic mutation in the Amyloid-β (Aβ) domain of the Amyloid-β precursor protein (APP) causes Alzheimer’s disease (AD) and confers unique biochemical characteristics to Aβ peptides. The aims of this thesis were to evaluate a transgenic model with the Arctic mutation, and to use it to gain new insights into the mechanisms of early (pre-plaque) and late-stage Aβ pathogenesis in AD. The Arctic mutation made Aβ more prone to aggregate, to accumulate in intracellular compartments and to form extracellular plaques when the models tg-ArcSwe and tg-Swe were compared. By inhibiting APP processing genetically or pharmacologically, the intraneuronal granular immunoreactivity with antibodies binding the Aβ domain was shown to largely represent Aβ, and not APP or APP-fragments. At two months of age, the intracellularly accumulated Aβ decreased rapidly, likely because it was still accessible to intracellular clearance. Extracellular Aβ deposits emerged at 5-6 months of age and the amyloid fibril structure was more compact than in tg-Swe. Moreover, Aβ deposits in tg-ArcSwe were more resistant to chemical extraction than those of established models carrying the Swedish APP mutation only, e.g. tg-Swe mice. The stability of deposits better reflects the biochemistry of senile plaques in AD. Thus, the tg-ArcSwe model may better predict the outcome of clinical trials, particularly therapies designed to enhance clearance of Aβ aggregates and deposits. Postmortem brain of Arctic mutation carriers contained extensive parenchymal plaque pathology. Differential immunostaining patterns with C- and N-terminal Aβ antibodies revealed a subset of plaques that were unique to the brains of Arctic mutation carriers. Aβ deposits in the cerebral vessel walls were congophilic and mainly composed of full-length Aβ. In contrast, N-terminally truncated Aβ was more prominent in the parenchymal plaques, all of which essentially lacked amyloid cores. A heterogeneous assembly of mutant and wild-type Aβ was shown to favor the formation of diffuse deposits in bitransgenic mice, and such mechanisms may at least partly explain observations of plaques lacking amyloid cores in postmortem Arctic mutant brain. In the bitransgenic mice, a low level of Arctic Aβ was sufficient to facilitate aggregation of wild-type Aβ. This observation, but also our findings of differences in amyloid fibril structure in tg-ArcSwe and tg-Swe, further highlights similarities between AD and prion disorders in which PrPsc refolds PrPc and facilitates fibril formation.
|
|
| 8. |
- Toor, Salman, et al.
(author)
-
SNIC Science Cloud (SSC): A national-scale cloud infrastructure for Swedish academia
- 2017
-
In: Proceedings - 13th IEEE International Conference on eScience, eScience 2017. - Los Alamitos, CA : IEEE Computer Society. ; , s. 219-227, s. 219-227
-
Conference paper (peer-reviewed)abstract
- The cloud computing paradigm have fundamentally changed the way computational resources are being offered. Although the number of large-scale providers in academia is still relatively small, there is a rapidly increasing interest and adoption of cloud Infrastructure-as-a-Service in the scientific community. The added flexibility in how applications can be implemented compared to traditional batch computing systems is one of the key success factors for the paradigm, and scientific cloud computing promises to increase adoption of simulation and data analysis in scientific communities not traditionally users of large scale e-Infrastructure, the so called long tail of science. In 2014, the Swedish National Infrastructure for Computing (SNIC) initiated a project to investigate the cost and constraints of offering cloud infrastructure for Swedish academia. The aim was to build a platform where academics could evaluate cloud computing for their use-cases. SNIC Science Cloud (SSC) has since then evolved into a national-scale cloud infrastructure based on three geographically distributed regions. In this article we present the SSC vision, architectural details and user stories. We summarize the experiences gained from running a nationalscale cloud facility into ten simple rules for starting up a science cloud project based on OpenStack. We also highlight some key areas that require careful attention in order to offer cloud infrastructure for ubiquitous academic needs and in particular scientific workloads.
|
|
