| 11. |
- van Schaarenburg, Rosanne A., et al.
(författare)
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Marked variability in clinical presentation and outcome of patients with C1q immunodeficiency
- 2015
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Ingår i: Journal of Autoimmunity. - : Elsevier BV. - 0896-8411 .- 1095-9157. ; 62, s. 39-44
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Globally approximately 60 cases of C1q deficiency have been described with a high prevalence of Systemic Lupus Erythematosus (SLE). So far treatment has been guided by the clinical presentation rather than the underlying C1q deficiency. Recently, it was shown that C1q production can be restored by allogeneic hematopoietic stem cell transplantation. Current literature lacks information on disease progression and quality of life of C1q deficient persons which is of major importance to guide clinicians taking care of patients with this rare disease.Methods: We performed an international survey, of clinicians treating C1q deficient patients. A high response rate of >70% of the contacted clinicians yielded information on 45 patients with C1q deficiency of which 25 are published.Results: Follow-up data of 45 patients from 31 families was obtained for a median of 11 years after diagnosis. Of these patients 36 (80%) suffer from SLE, of which 16 suffer from SLE and infections, 5 (11%) suffer from infections only and 4 (9%) have no symptoms. In total 9 (20%) of the C1q deficient individuals had died. All except for one died before the age of 20 years. Estimated survival times suggest 20% case-fatality before the age of 20, and at least 50% of patients are expected to reach their middle ages.Conclusion: Here we report the largest phenotypic data set on C1q deficiency to date, revealing high variance; with high mortality but also a subset of patients with an excellent prognosis. Management of C1q deficiency requires a personalized approach.
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| 18. |
- Ahlin, Gustav, et al.
(författare)
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Structural requirements for drug inhibition of the liver specific human organic cation transport protein 1
- 2008
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 51:19, s. 5932-5942
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Tidskriftsartikel (refereegranskat)abstract
- The liver-specific organic cation transport protein (OCT1; SLC22A1) transports several cationic drugs including the antidiabetic drug metformin and the anticancer agents oxaliplatin and imatinib. In this study, we explored the chemical space of registered oral drugs with the aim of studying the inhibition pattern of OCT1 and of developing predictive computational models of OCT1 inhibition. In total, 191 structurally diverse compounds were examined in HEK293-OCT1 cells. The assay identified 47 novel inhibitors and confirmed 15 previously known inhibitors. The enrichment of OCT1 inhibitors was seen in several drug classes including antidepressants. High lipophilicity and a positive net charge were found to be the key physicochemical properties for OCT1 inhibition, whereas a high molecular dipole moment and many hydrogen bonds were negatively correlated to OCT1 inhibition. The data were used to generate OPLS-DA models for OCT1 inhibitors; the final model correctly predicted 82% of the inhibitors and 88% of the noninhibitors of the test set.
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| 19. |
- Ahlin, Karin, 1963-
(författare)
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Benefits of Digital Technical Information
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In our daily work life, we use a wealth of information, including a category of information produced as a part of products and their life-cycle phases, named digital technical information (DTI). Manufacturing organizations focus more often on the product than on DTI, because DTI’s impact seems almost invisible, despite its crucial role to the product and its life-cycle phases, development, production, maintenance, and destruction. Hence, the aim of this thesis is to describe DTI’s benefits and the research questions: “What are the benefits of the DTI?” and “What are the perceptions of how to measure benefits of DTI?” The thesis contains five studies related to identifying and measuring DTI’s benefits. The empirical material is based on semi-structured interviews and group interviews within five organizations and a survey among manufacturing organizations in Sweden.I used three characteristics of the DTI and two pairs of previously known benefit categories to analyse the benefits. The analysis shows that the benefits are recognized in the particular product’s life cycle phase where the DTI is published. However, the DTI continues to offer benefits in the product’s other life cycle phases. In relationship to the product, the benefits evolve from supporting an individual product to supporting more general product lines or all products and a more complex product is said to increase DTI’s benefits. DTI’s structure adds benefits as synthesized or aggregated DTI, where the DTI is synthesized or aggregated automatically or manually. The categorization predetermined benefits related to the change are less numerous than the emerging benefits. The predetermined benefits are strategic by nature, and the emerging ones are mainly used to achieve operational goals. Measuring DTI’s benefits is of importance for a formal comparison of its development and is of special interest for managers. Perceptions from the initial stages on how to measure show that to establish common interpretations among the stakeholders of the measurement process is of importance, especially when it comes to what is viewed as a benefit. The benefits are viewed as intangible by the respondents, which creates difficulties when one is evaluating, using conventional measurement methods. The only perceived way to measure is when DTI reduces co-worker’s workload and efficiency is achieved. The thesis’s contribution to academia consists of the analysis of DTI’s benefits, showing details of the relationships between the DTI and its benefits. For practice, the contributions focus on the systematic evaluation process, which can be used for further development of the DTI and comparison of the evolvement of the DTI itself and relating to other resources. One proposal for future research is to use the analysed benefits and compare various approaches to digitizing DTI, e.g. Industry 4.0. Another proposal is to list, in detail, various ways on how to measure DTI’s benefits and their usefulness. The latter can positively impact on any intangible benefits due to the general approach we have established of how to measure those benefits.
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| 20. |
- Ahlin, Sofie, 1985, et al.
(författare)
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Bile acid changes after metabolic surgery are linked to improvement in insulin sensitivity
- 2019
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Ingår i: British Journal of Surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 106:9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Metabolic surgery is associated with a prompt improvement in insulin resistance, although the mechanism of action remains unknown. The literature on bile acid changes after metabolic surgery is conflicting, and insulin sensitivity is generally assessed by indirect methods. The aim of this study was to investigate the relationship between improvement in insulin sensitivity and concentration of circulating bile acids after biliopancreatic diversion (BPD) and Roux-en-Y gastric bypass (RYGB). Methods: This was a prospective observational study of nine patients who underwent BPD and six who had RYGB. Inclusion criteria for participation were a BMI in excess of 40 kg/m(2), no previous diagnosis of type 2 diabetes and willingness to participate. Exclusion criteria were major endocrine diseases, malignancies and liver cirrhosis. Follow-up visits were carried out after a mean(s.d.) of 185.3(72.9) days. Fasting plasma bile acids were assessed by ultra-high-performance liquid chromatography coupled with a triple quadrupole mass spectrometer, and insulin sensitivity was measured by means of a hyperinsulinaemic-euglycaemic clamp. Results: A significant increase in all bile acids, as well as an amelioration of insulin sensitivity, was observed after metabolic surgery. An increase in conjugated secondary bile acids was significantly associated with an increase in insulin sensitivity. Only the increase in glycodeoxycholic acid was significantly associated with an increase in insulin sensitivity in analysis of individual conjugated secondary bile acids. Conclusion: Glycodeoxycholic acid might drive the improved insulin sensitivity after metabolic surgery.
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