| 1. |
- Sund, Johan, et al.
(författare)
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Binding Site Preorganization and Ligand Discrimination in the Purine Riboswitch
- 2015
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Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 119:3, s. 773-782
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Tidskriftsartikel (refereegranskat)abstract
- The progress of RNA research has suggested a wide variety of RNA molecules as possible targets for pharmaceutical drug molecules. Structure-based computational methods for predicting binding modes and affinities are now important tools in drug discovery, but these methods have mainly been focused on protein targets. Here we employ molecular dynamics free-energy perturbation calculations and the linear interaction energy method to analyze the energetics of ligand binding to purine riboswitches. Calculations are carried out for 14 different purine complexes with the guanine and adenine riboswitches in order to examine their ligand recognition principles. The simulations yield binding affinities in good agreement with experimental data and rationalize the selectivity of the riboswitches for different ligands. In particular, it is found that these receptors have an unusually high degree of electrostatic preorganization for their cognate ligands, and this effect is further quantified by explicit free-energy calculations, which show that the standard electrostatic linear interaction energy parametrization is suboptimal in this case. The adenine riboswitch specifically uses the electrostatic preorganization to discriminate against guanine by preventing the formation of a G-U wobble base pair.
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| 2. |
- Gari, Hala, et al.
(författare)
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Amperometric In Vitro Monitoring of Penetration through Skin Membrane
- 2015
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Ingår i: Electroanalysis. - : Wiley. - 1040-0397 .- 1521-4109. ; 27:1, s. 111-117
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to demonstrate that penetration of quercetin, hydrogen peroxide and ascorbic acid through skin membranes can be monitored amperometrically. Skin membrane was fixed on the top of chemically modified electrodes and penetration of the appropriate compound was registered as electrode current. The methodology allows the study of penetration from solution as well as from pharmaceutical creams. From real-time measurements of electrode current, fluxes and diffusion coefficients of mentioned compounds in skin membranes have been estimated.
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| 3. |
- Holsti, Mari, 1963-, et al.
(författare)
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Circulating Vascular Basement Membrane Fragments are Associated with the Diameter of the Abdominal Aorta and Their Expression Pattern is Altered in AAA Tissue
- 2018
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Ingår i: European Journal of Vascular and Endovascular Surgery. - : Saunders Elsevier. - 1078-5884 .- 1532-2165. ; 56:1, s. 110-118
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Abdominal aortic aneurysm (AAA) is characterised by enhanced proteolytic activity, and extracellular matrix (ECM) remodelling in the vascular wall. Type IV and XVIII collagen/endostatin are structural proteins in vascular basement membrane (VBM), a specialised ECM structure. Here the association between plasma levels of these collagens with the aortic diameter and expansion rate is studied, and their expression in aortic tissue characterised. Methods: This was a retrospective population based cohort study. Type IV and XVIII collagen/endostatin were analysed in plasma by ELISA assay in 615 men, divided into three groups based on the aortic diameter: 1) normal aorta <= 25 mm, 2) sub-aneurysmal aorta (SAA) 26-29 mm, and 3) AAA >= 30 mm. Follow up data were available for 159 men. The association between collagen levels and aortic diameter at baseline, and with the expansion rate at follow up were analysed in ordinal logistic regression and linear regression models, controlling for common confounding factors. Tissue expression of the collagens was analysed in normal aorta (n = 6) and AAA (n = 6) by immunofluorescence. Results: Plasma levels of type XVIII collagen/endostatin (136 ng/mL [SD 29] in individuals with a normal aorta diameter, 154 ng/ml [SD 45] in SAA, and 162 ng/ml [SD 46] in AAA; p = .001) and type IV collagen (105 ng/mL [SD 42] normal aorta, 124 ng/ml [SD 46] SAA, and 127 ng/ml [SD 47] AAA; p = .037) were associated with a larger aortic diameter. A significant association was found between the baseline levels of type XVIII/endostatin and the aortic expansion rate (p = .035), but in the multivariable model, only the initial aortic diameter remained significantly associated with expansion (p = .005). Altered expression patterns of both collagens were observed in AAA tissue. Conclusion: Plasma levels of circulating type IV and XVIII collagen/endostatin increase with AAA diameter. The expression pattern of VBM proteins is altered in the aneurysm wall.
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| 4. |
- Sund, Louise, 1970-, et al.
(författare)
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Ethical reflections
- 2017
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Ingår i: Paper presented at the symposium: A Transactional Approach on ESD Research (Part 1)..
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Konferensbidrag (refereegranskat)abstract
- This contribution builds on an analytical approach using Dewey’s thoughts on morals and ethics to address how we acquire our morals, how we can reflect on moral situations, and how ethical reflections are visible in practice. In the study (Sund and Öhman, 2014) we investigate the variety of ethical reflections that emerge when a group of Swedish teachers participate in a study visit to Central America. Following Dewey, we investigated how a teacher, in interaction with others, finds a way to morally reason and co-ordinate with her or his surroundings. In this social co-construction things are literally made common—we socially construct the meaning of right and wrong and what works better in our lives, given the current problematic or situation.The study illustrates important possibilities for using Dewey’s perspective on morals and ethics in empirical studies. Firstly, ethical reflections are not hidden within humans’ minds but are available for empirical investigations of actions. Secondly, morality arises in relation to others and therefore needs to be investigated in relation to concrete and lived experiences. Thirdly, it demonstrates how ethical reflections can be investigated as processes of continuity and change. Lastly, the result underlines Dewey’s point that we need to move away from normative ethical theories and instead deepen the understanding of how humans try to co-ordinate their everyday actions with other people.
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| 5. |
- Sund, Louise, 1970-, et al.
(författare)
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Ethical Reflections on Intercultural interchanges
- 2016
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Ingår i: Paper presented at the symposium: A transactional perspective on meaning-making. Part 1. Ethical participation and ethical reflections..
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Konferensbidrag (refereegranskat)abstract
- The purpose of this symposium is to present a range of studies which use Dewey’s transactional perspective on meaning-making and practical epistemologies of education. In his influential work Democracy and Education (1916) John Dewey states that the basic role of education is to introduce the new generation to the knowledge and customs of previous members of a society. But a society consists of many practices and since different practices are based on different purposes, values and interests, the ideas that are held as true and good and the justified ways of making meaning differ between practices (Rorty 1991). To be a competent member of a society thus means being able to understand and make meanings in relation to a number of different practical epistemologies but also being capable of being critical of such epistemologies. The research group SMED (Studies of Meaning-making in Educational Discourses) has been engaged in the development of a methodology for analysing meaning-making processes where people are introduced to different practical epistemologies in educational settings. The methodology builds on John Dewey’s pragmatic philosophy and especially his concept of transaction (Dewey & Bentley 1949/1991). This perspective overcomes the methodological problems connected with the dualistic tendencies that trouble many other approaches to learning and classroom interactions. Within this approach meaning is not treated as something that exists within things themselves or in the minds of human beings, but is seen as the relations to the environment that is created in the processes of doing and undergoing the consequences of action. Such coordination is not restricted to knowledge but also involves ethical and aesthetical relations to the environment. Learning can thus be investigated in terms of actions, within a set of different practical epistemologies.
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| 6. |
- Vackerberg, Nicoline, et al.
(författare)
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What is best for Esther? Building improvement coaching capacity with and for users in health and social Care-A case study
- 2016
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Ingår i: Quality Management in Health Care. - : LIPPINCOTT WILLIAMS & WILKINS. - 1063-8628 .- 1550-5154. ; 25:1, s. 53-60
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Tidskriftsartikel (refereegranskat)abstract
- While coaching and customer involvement can enhance the improvement of health and social care, many organizations struggle to develop their improvement capability; it is unclear how best to accomplish this. We examined one attempt at training improvement coaches. The program, set in the Esther Network for integrated care in rural Jonkoping County, Sweden, included eight 1-day sessions spanning 7 months in 2011. A senior citizen joined the faculty in all training sessions. Aiming to discern which elements in the program were essential for assuming the role of improvement coach, we used a case-study design with a qualitative approach. Our focus group interviews included 17 informants: 11 coaches, 3 faculty members, and 3 senior citizens. We performed manifest content analysis of the interview data. Creating will, ideas, execution, and sustainability emerged as crucial elements. These elements were promoted by customer focusembodied by the senior citizen trainershared values and a solution-focused approach, by the supportive coach network and by participants' expanded systems understanding. These elements emerged as more important than specific improvement tools and are worth considering also elsewhere when seeking to develop improvement capability in health and social care organizations.
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| 7. |
- Valachis, Antonis, 1984-, et al.
(författare)
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Effect of selective serotonin reuptake inhibitors use on endocrine therapy adherence and breast cancer mortality : a population-based study
- 2016
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Ingår i: Breast Cancer Research and Treatment. - : Kluwer Academic/Plenum Publishers. - 0167-6806 .- 1573-7217. ; 159:2, s. 293-303
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of the study was to investigate whether the concomitant use of selective serotonin reuptake inhibitors (SSRI) with tamoxifen influences the risk of death due to breast cancer, and we also investigated the association between SSRI use and adherence to oral endocrine therapy (ET). We analyzed data from BCBaSe Sweden, which is a database created by the data linkage of Registries from three different regions of Sweden. To investigate the association between ET adherence and SSRI use, we included all women who were diagnosed with non-distant metastatic ER-positive invasive breast cancer from July 2007 to July 2011 and had at least one dispensed prescription of oral tamoxifen or aromatase inhibitor. To investigate the role of concurrent administration of SSRI and tamoxifen on breast cancer prognosis, we performed a nested case-control study. In the adherence cohort, 9104 women were included in the analyses. Women who received SSRI, either before or after breast cancer diagnosis, were at higher risk for low adherence to ET. However, when the overlapping period between SSRI use and ET was >50 %, no excess risk for low adherence was observed. Non-adherence (<80 %) to ET was significantly associated with worse breast cancer survival (OR 4.07; 95 % CI 3.27-5.06). In the case-control study, 445 cases and 11125 controls were included. The concomitant administration of SSRI and tamoxifen did not influence breast cancer survival, neither in short-term (OR 1.41; 95 % CI 0.74-2.68) nor in long-term SSRI users (OR 0.85; 95 % CI 0.35-2.08). Concomitant SSRI and tamoxifen use does not seem to increase risk for death due to breast cancer. Given the positive association between continuing antidepressive pharmacotherapy for a longer period of time and adherence to ET, it is essential to capture and treat depression in breast cancer patients to secure adherence to ET.
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| 8. |
- Wadsten, Charlotta, et al.
(författare)
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A validation of DCIS registration in a population-based breast cancer quality register and a study of treatment and prognosis for DCIS during 20 years
- 2016
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Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 55:11, s. 1338-1343
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Sweden has a long history of population-based cancer registration. The aim of our study was to assess the validity of DCIS registration in a regional Breast Cancer Quality Register (BCQR) and to analyze trends in incidence, treatment and outcome of DCIS, over a 20-year period.MATERIAL AND METHODS: All patients with a diagnosis of primary DCIS reported in the BCQR of the Uppsala-Örebro healthcare region in Sweden 1992-2012 were included. Three hundred women were randomly selected and their medical records were compared to register data. The study period was divided into four time periods.RESULTS: A total of 2952 women were registered with a DCIS diagnosis. In the final validation cohort of 295 patients, 23 were found to have either recurrent DCIS or invasive breast cancer and eight had LCIS. The completeness and validity of key variables were 91-99%. Twenty of 31 local recurrences were registered (65%).The proportion of DCIS to all breast cancers was 9.5%. Tumor size increased over time. The frequency of mastectomy increased from 23.0% to 39.0%. The proportion of patients receiving radiotherapy after breast conserving surgery increased from 30.1% to 67.6%. The reported local recurrence rate was 9.7% after 10 years. Reported recurrences after BCS and mastectomy were 12.0 and 7.0%, respectively. The recurrence rate did not differ between women undergoing BCS with or without radiotherapy.CONCLUSION: Only 89.5% of reported DCIS was a primary pure DCIS. The completeness of primary treatment and tumor data was high. The proportion of reported local recurrences was disappointingly low, 65%. The proportion of DCIS was stable over time with a trend towards more intensified treatment. The reported recurrence rate was low independent of treatment and can reflect adequate patient selection, but also over treatment. Our results address the necessity to validate register data on a regular basis.
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| 9. |
- Westman, Gabriel, 1977-, et al.
(författare)
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Clinical significance of IgM and IgA class anti-NMDAR antibodies in herpes simplex encephalitis
- 2018
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Ingår i: Journal of Clinical Virology. - : Elsevier BV. - 1386-6532 .- 1873-5967. ; 103, s. 75-80
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Tidskriftsartikel (refereegranskat)abstract
- Background: Herpes simplex encephalitis (HSE) is a devastating disease, often leaving patients with severe disabilities. It has been shown that IgG anti-N-methyl-o-aspartate receptor (NMDAR) antibodies appear in approximately 25% of HSE patients and could be associated with impaired recovery of cognitive performance. Objectives: To characterize the prevalence of IgM and IgA anti-NMDAR antibodies in HSE patients, in relation to subsequent development of IgG anti-NMDAR and correlation to cognitive performance. Study design: A total of 48 subjects were included from a previously described cohort of patients with HSE verified by HSV-1 PCR. Cerebrospinal fluid (CSF) and serum samples drawn close to onset of disease, after 14-21 days of iv aciclovir treatment and after 90 days of follow-up, were analyzed for the presence of IgM and IgA anti-NMDAR, and related to IgG anti-NMDAR. Antibody levels were correlated to the recovery of cognitive performance, as estimated by the Mattis Dementia Rating Scale (MDRS), for a total of 24 months. Results: In total, 27 of 48 (56%) study subjects were anti-NMDAR positive, defined as the presence of IgG (12/ 48, 25%), IgM (14/48, 29%) or IgA (13/48, 27%) antibodies in CSF and/or serum. IgM or IgA anti-NMDAR did not predict subsequent IgG autoimmunization and did not correlate to cognitive outcome. IgG anti-NMDAR serostatus, but not antibody titers, correlated to impaired recovery of cognitive performance. Conclusions: A majority of HSE patients develop IgG, IgM or IgA anti-NMDAR antibodies. However, the predictive value and clinical relevance of non-IgG isotypes remains to be shown in this setting.
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| 10. |
- Åsa, Weinholt
(författare)
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Exploring Collaboration Between the Fire and Rescue Service and New Actors : Cost-efficiency and Adaptation
- 2015
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The emergency services serves an important purpose in society by ensuring that people in need, regardless of their geographical location, receives help when they fall victims to undesirable incidents. Existing resources are however often limited and concentrated to urban areas making travel distances to remote areas long. Local authorities are also facing budget constraints and clients are becoming more demanding. This means that the emergency services need to do more, but with less resources. Collaboration with new actors has therefore been proposed as a solution. There exist several actors with basic knowledge in both fire suppression or medical treatment that might be able to contribute at an early stage in order to reduce response time and provide help to citizens in need. However, little research has been dedicated to investigating the possibilities and the potential of new collaborative practices in every day accidents.In this thesis collaboration between new actors and the fire and rescue service (FRS) in Sweden is studied. The aim is to analyze whether collaborative practices leads to an increased cost-efficiency, for the FRS and society as a whole. The thesis also aims to analyze how traditional actors and new actors adapt to collaborative practices.For evaluating cost-efficiency in the FRS stochastic frontier analysis is used and for analyzing the societal effects cost-benefit analysis is applied. In total three cases are studied; (1) security officers assisting the FRS in fire alarms (2) home care nurses collaborating with the FRS in medical alarms and (3) citizens responding to FRS-alarms through SMS.The results do not show that collaboration have led to increased cost-efficiency in the FRS during the studied time period. However, despite that no evidence for increased cost-efficiency is found in the FRS, there are several societal gains from collaborating related to e.g. equity, quality and effectiveness. And the costs for implementing collaborative arrangements are relatively low. It is however argued that to be able to get the most out of collaboration more emphasis should be put on building common platforms, where the different organizations and actors can communicate, share experiences, organize joint training sessions and actually collaborate. Today interaction outside the rescue site hardly exist between the collaborative partners; the actual collaboration between the FRS and the new actors is limited only to the response phase. Also, the FRS do not adapt their bureaucratic structures to collaborate with the new actors. Instead the changes associated with collaboration affect mainly the new actors, as an addition to their regular duties. Factors related to discretion, professional identity and personal motivation are identified as important for understanding how new actors adapt to collaboration.
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| 11. |
- Öhman, Johan, 1961-, et al.
(författare)
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Ethical reflections
- 2017
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Konferensbidrag (refereegranskat)
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