| 1. |
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| 2. |
- Moberg, Christina, et al.
(författare)
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De unga gör helt rätt när de stämmer staten
- 2022
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Ingår i: Aftonbladet. - 1103-9000.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- 1 620 forskare och lärare i forskarvärlden: Vi ställer oss bakom Auroras klimatkrav
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| 6. |
- Springett, Jane, 1952-, et al.
(författare)
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Närsjukvård : bakgrund, erfarenheter och pilotstudie
- 2005
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Närsjukvård är ett centralt begrepp i ett förändringsarbete som för genomförs i nordöstra Skåne för att utveckla hälso- och sjukvårdsväsendet. Det ingår därmed som en av de centrala delarna av Region Skånes vision om hälso- och sjukvård: Skånsk livskraft – vård och hälsa. Syftet med denna rapport är att ge en bakgrund till begreppet (Del A) och att presentera en del preliminära rön beträffande hur olika aktörer i nordöstra Skåne uppfattar begreppet (Del B). Del A ger en översikt kring ursprunget till begreppet Närsjukvård inom ramen för de förändringar i hälso- och sjukvården som sker i Sverige i stort. Den beskriver sedan vilka slags förändringar som har planerats på politisk nivå och som nu håller på att genomföras under detta paraplybegrepp, nationellt, regionalt och lokalt. För detta syfte används statliga dokument och publicerade utvärderingsstudier i stor utsträckning som källmaterial. Denna del ska därför inte ses som en heltäckande översikt. Del B inriktas på att belysa hur långt förverkligandet av idén om Närsjukvård har kommit inom regionen. Avsnittet är en kartläggning av olika aktörers förståelse av Närsjukvård i den nordöstra delen av Region Skåne. Forskningsfrågorna inriktades på hur folk pratade om Närsjukvård, det vill säga på hur de förstod och använde begreppet.
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| 7. |
- Springett, Jane, et al.
(författare)
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Närsjukvård : bakgrund, erfarenheter och pilotstudie
- 2005
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- Närsjukvård är ett centralt begrepp i ett förändringsarbete som för genomförs i nordöstra Skåne för att utveckla hälso- och sjukvårdsväsendet. Det ingår därmed som en av de centrala delarna av Region Skånes vision om hälso- och sjukvård: Skånsk livskraft – vård och hälsa. Syftet med denna rapport är att ge en bakgrund till begreppet (Del A) och att presentera en del preliminära rön beträffande hur olika aktörer i nordöstra Skåne uppfattar begreppet (Del B). Del A ger en översikt kring ursprunget till begreppet Närsjukvård inom ramen för de förändringar i hälso- och sjukvården som sker i Sverige i stort. Den beskriver sedan vilka slags förändringar som har planerats på politisk nivå och som nu håller på att genomföras under detta paraplybegrepp, nationellt, regionalt och lokalt. För detta syfte används statliga dokument och publicerade utvärderingsstudier i stor utsträckning som källmaterial. Denna del ska därför inte ses som en heltäckande översikt. Del B inriktas på att belysa hur långt förverkligandet av idén om Närsjukvård har kommit inom regionen. Avsnittet är en kartläggning av olika aktörers förståelse av Närsjukvård i den nordöstra delen av Region Skåne. Forskningsfrågorna inriktades på hur folk pratade om Närsjukvård, det vill säga på hur de förstod och använde begreppet.
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| 8. |
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| 9. |
- Axfors, Cathrine, et al.
(författare)
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Association between convalescent plasma treatment and mortality in COVID-19 : a collaborative systematic review and meta-analysis of randomized clinical trials
- 2021
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Ingår i: BMC Infectious Diseases. - : BioMed Central (BMC). - 1471-2334. ; 21:1
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Forskningsöversikt (refereegranskat)abstract
- Background: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, ). Methods: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I-2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Conclusions: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.
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| 10. |
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| 11. |
- Bernin, Diana, 1979, et al.
(författare)
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Real time MRI to elucidate the functionality of coating films intended for modified release
- 2019
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Ingår i: Journal of Controlled Release. - : Elsevier BV. - 0168-3659 .- 1873-4995. ; 311-312, s. 117-124
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Tidskriftsartikel (refereegranskat)abstract
- Polymer films based on mixtures of ethyl cellulose (EC) and hydroxypropyl cellulose (HPC) have been widely used to coat pellets and tablets to modify the release profile of drugs. For three different EC/HPC films we used 1H and 19F MRI in combination with a designed release cell to monitor the drug, polymer and water in 5 dimensional (5D) datasets; three spatial, one diffusion or relaxation and a temporal dimension, in real time. We observed that the water inflow through the films correlated with the initiation of the dissolution of the drug in the tablet beneath the film. Leaching of the pore forming HPC further accelerated water penetration and resulted in a drug release onset after a hydrostatic pressure was generated below the film indicated by positional changes of the film. For the more permeable film, both water ingress and drug egress showed a large variability of release over the film surface indicating the heterogeneity of the system. Furthermore, the 1H diffusion dataset revealed the formation of a gel layer of HPC at the film surface. We conclude that the setup presented provides a significant level of details, which are not achieved with traditional methods.
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| 12. |
- Bill, Susanna, et al.
(författare)
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Rethinking User Involvement in the Front End of Healthcare Innovation
- 2011
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Konferensbidrag (refereegranskat)abstract
- The purpose of this paper is to share insights from an empirical study within the Swedish healthcare system, based on a case study of the largest business unit of a Swedish medical technology company and its key customer segment. The study involving a Swedish medical technology company and three Swedish hospitals indicates need to move away from an archetypical, largely homogeneous view of the user, towards a more flexible, heterogeneous user perspective. Following from that insight the paper outlines a preliminary model aimed at improving the conditions of the firm for user involvement in the front end of healthcare innovation. In the proposed model, different users are brought to the foreground in different parts of the front-end innovation process. The research performed aimed at putting the business unit in a more beneficial position to involve users in the front end of innovation by increasing their understanding of a) which user types they actually have access to, b) which roles that different user types may take in the various stages of the innovation front-end.
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| 13. |
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| 14. |
- Buli, Benti Geleta, et al.
(författare)
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Trends in psychosomatic symptoms among adolescents and the role of lifestyle factors
- 2024
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Ingår i: BMC Public Health. - 1471-2458. ; 24
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Tidskriftsartikel (refereegranskat)abstract
- Background Adolescent mental health problems are on the rise globally, including in Sweden. One indicator of this trend is increased psychosomatic symptoms (PSS) over time. Lifestyle factors such as physical activity (PA), diet, smoking, and alcohol consumption may influence the time trends in PSS; however, the evidence base is scarce. The aim of this study was to investigate associations between time trends in PSS and lifestyle factors.Methods The study was based on data collected from a nationally representative sample of 9,196 fifteen-year-old boys and girls in Sweden using the Health Behavior in School-aged Children (HBSC) symptom checklist. The sample comprised nearly equal proportions of girls (50.5%) and boys. The lifestyle factors examined in this study included PA, regular breakfast intake, consumption of fruits, vegetables, sweets, or soft drinks, smoking, and alcohol drunkenness. We used data from 2002 to 2018 and stratified by family affluence scale (FAS) to demonstrate how the associations varied among the FAS groups. We fitted separate regression models for the high- and low-FAS groups, where interaction terms between the year of survey and each lifestyle factor were used to estimate the level and direction of associations between the factors and trends in PSS.Results There was a generally increasing trend in PSS mean scores from 2.26 in 2002 to 2.49 in 2018 (p <.001). The changes in each survey year compared to the average mean scores during the preceding years were significant in all years except 2010. Regular breakfast intake, daily fruit and vegetable consumption, and higher PA were associated with lower PSS mean scores, while smoking and drunkenness had opposite associations with PSS. The only significant interaction between survey year and the lifestyle factors was observed regarding drunkenness in the high FAS group, suggesting that the association between trends in PSS and the experience of getting drunk at least twice got stronger over time (B = 0.057; CI:0.016, 0.097; p <.01).Conclusions The results indicate increasing trends in PSS among young people in Sweden from 2002 to 2018, with a significant increase observed among adolescents in the high FAS group who reported getting drunk on at least two occasions.
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| 15. |
- Carlsen, Hanne Krage, et al.
(författare)
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Birch pollen, air pollution and their interactive effects on airway symptoms and peak expiratory flow in allergic asthma during pollen season - a panel study in Northern and Southern Sweden
- 2022
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Ingår i: Environmental health. - : Springer Science and Business Media LLC. - 1476-069X. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Evidence of the role of interactions between air pollution and pollen exposure in subjects with allergic asthma is limited and need further exploration to promote adequate preventive measures. The objective of this study was to assess effects of exposure to ambient air pollution and birch pollen on exacerbation of respiratory symptoms in subjects with asthma and allergy to birch. Methods: Thirty-seven subjects from two Swedish cities (Gothenburg and Umea) with large variation in exposure to both birch-pollen and air pollutants, participated in the study. All subjects had confirmed allergy to birch and self-reported physician-diagnosed asthma. The subjects recorded respiratory symptoms such as rhinitis or eye irritation, dry cough, dyspnoea, the use of any asthma or allergy medication and peak respiratory flow (PEF), daily for five consecutive weeks during two separate pollen seasons and a control season without pollen. Nitrogen oxides -(NOx), ozone -(O-3), particulate matter -(PM2.5), birch pollen counts, and meteorological data were obtained from an urban background monitoring stations in the study city centres. The data were analysed using linear mixed effects models. Results: During pollen seasons all symptoms and medication use were higher, and PEF was reduced in the subjects. In regression analysis, exposure to pollen at lags 0 to 2 days, and lags 0 to 6 days was associated with increased ORs of symptoms and decreased RRs for PEF. Pollen and air pollution interacted in some cases; during low pollen exposure, there were no associations between air pollution and symptoms, but during high pollen exposure, -O-3 concentrations were associated with increased OR of rhinitis or eye irritation, and -PM2.5 concentrations were associated with increased ORs of rhinitis or eye irritation, dyspnea and increased use of allergy medication. Conclusions: Pollen and air pollutants interacted to increase the effect of air pollution on respiratory symptoms in allergic asthma. Implementing the results from this study, advisories for individuals with allergic asthma could be improved, minimizing the morbidities associated with the condition.
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| 16. |
- Carvalho, Raquel N., et al.
(författare)
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Mixtures of chemical pollutants at European legislation safety concentrations : how safe are they?
- 2014
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Ingår i: Toxicological Sciences. - : Oxford University Press (OUP). - 1096-6080 .- 1096-0929. ; 141:1, s. 218-233
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Tidskriftsartikel (refereegranskat)abstract
- The risk posed by complex chemical mixtures in the environment to wildlife and humans is increasingly debated, but has been rarely tested under environmentally relevant scenarios. To address this issue, two mixtures of 14 or 19 substances of concern (pesticides, pharmaceuticals, heavy metals, polyaromatic hydrocarbons, a surfactant, and a plasticizer), each present at its safety limit concentration imposed by the European legislation, were prepared and tested for their toxic effects. The effects of the mixtures were assessed in 35 bioassays, based on 11 organisms representing different trophic levels. A consortium of 16 laboratories was involved in performing the bioassays. The mixtures elicited quantifiable toxic effects on some of the test systems employed, including i) changes in marine microbial composition, ii) microalgae toxicity, iii) immobilization in the crustacean Daphnia magna, iv) fish embryo toxicity, v) impaired frog embryo development, and vi) increased expression on oxidative stress-linked reporter genes. Estrogenic activity close to regulatory safety limit concentrations was uncovered by receptor-binding assays. The results highlight the need of precautionary actions on the assessment of chemical mixtures even in cases where individual toxicants are present at seemingly harmless concentrations.
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| 17. |
- Cassel, Anders, et al.
(författare)
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On Perception Safety Requirements and Multi Sensor Systems for Automated Driving Systems
- 2020
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Ingår i: SAE technical paper series. - 400 Commonwealth Drive, Warrendale, PA, United States : SAE International. - 0148-7191. ; 2020-April:April
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Tidskriftsartikel (refereegranskat)abstract
- One major challenge in designing SAE level 3-5 Automated Driving Systems (ADS) is to define requirements for the perception system that would enable argumentation for safe operation. The safety requirements on the perception system can only be fulfilled through redundancy in the sensor hardware. It is, however, a challenge to specify the redundancy that is required in the sensor system. Safe operation for an ADS is significantly more difficult compared to advanced driver assistance systems (ADAS). The safety argumentation for ADAS typically argues that in case of a failure in the sensor array a fail-silent behavior is acceptable because the human driver can take control of the vehicle back. This argumentation however is not possible when developing level 4 or higher automation. This paper investigates prerequisites for applying a systematic methodology for analyzing redundancy in a multi-sensor system and the relation to a conceptual ADS functional architecture. This analysis must address the complexity that comes with partially overlapping sensor data from different sensors and considers variations in performance and characteristics due to changes in the environmental conditions. The paper introduces the term incomplete redundancy and presents a systematic methodology for analyzing redundancy. The aim is to provide arguments for how several sensors in a system, when appropriately combined, meet an assigned safety requirement on a higher level. Each sensor will then be assigned a certain responsibility and contributes with a sub-set of information. A set of questions of importance to address as a foundation for such a methodology are defined and discussed. The definitions of redundancy and independence between sensors are discussed as well as contract-based functional safety to adapt to different environmental and operating conditions.
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| 18. |
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| 19. |
- Danielsson, Susanna, 1964, et al.
(författare)
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Epilepsy in young adults with autism: a prospective population-based follow-up study of 120 individuals diagnosed in childhood.
- 2005
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Ingår i: Epilepsia. - : Wiley. - 0013-9580 .- 1528-1167. ; 46:6, s. 918-923
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Little is known about the long-term outcome of epilepsy in autism and the epilepsy characteristics of adults with autism. This prospective population-based study was conducted in an attempt to point out differences on a group basis between adults with autism with or without epilepsy, and to describe the occurrence, the seizure characteristics, and the outcome of epilepsy in autism. METHODS: One hundred eight of 120 individuals with autism diagnosed in childhood and followed up prospectively for a period of 13-22 years were reevaluated at ages 17-40 years. As adults, the majority had mental retardation and autistic disorder or autistic-like condition. Interviews were performed with the caretakers of 42 of 43 individuals with a history of epilepsy, and their medical records were reviewed. RESULTS: Adults with autism and mental retardation constituted a severely disabled group. On a group basis, both the cognitive level and the adaptive behavior level were lower in the epilepsy group than in the nonepilepsy group (p<0.05). In all, 38% had epilepsy. One third had epilepsy onset before age 2 years. Remission of epilepsy was seen in 16%. Partial seizures with or without secondarily generalized seizures were the dominating seizure type. CONCLUSIONS: In a community sample of individuals with autism followed up from childhood through to adult age, one of three had epilepsy since childhood/adolescence. Severe mental retardation and autism are significantly associated with epilepsy, especially in female patients. Seizure frequency has a great impact on the individuals' lives. Specialist medical care is needed in this severely communication-disabled population.
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| 20. |
- Danielsson, Susanna, 1964, et al.
(författare)
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Lack of effects of vagus nerve stimulation on drug-resistant epilepsy in eight pediatric patients with autism spectrum disorders: a prospective 2-year follow-up study.
- 2008
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Ingår i: Epilepsy & Behavior. - : Elsevier BV. - 1525-5050. ; 12:2, s. 298-304
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Tidskriftsartikel (refereegranskat)abstract
- Vagus nerve stimulation (VNS) therapy has been reported to reduce seizure frequency in some children with drug-resistant epilepsy who are not suitable candidates for epilepsy surgery. It has been suggested that there may be positive cognitive and/or behavioral effects independent of seizure control. We describe the effects of VNS with respect to seizure frequency, cognition, and autistic symptoms and behavior in eight children and adolescents with medically intractable epilepsy and autism. In comparison to baseline, seizure frequency had not decreased in anyone in our series at the 2-year follow-up. In three cases, minor improvements in general functioning were noted, but there were no positive cognitive effects. This open prospective pilot study highlights the need for more prospective studies to prevent false expectations of improvement in this severely disabled group.
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| 21. |
- Danielsson, Susanna, 1964, et al.
(författare)
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Psychopathology, psychosocial functioning, and IQ before and after epilepsy surgery in children with drug-resistant epilepsy.
- 2009
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Ingår i: Epilepsy & Behavior. - : Elsevier BV. - 1525-5050. ; 14:2, s. 330-337
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Tidskriftsartikel (refereegranskat)abstract
- This is a prospective study of a consecutive series of children undergoing epilepsy surgery. The main aims were to evaluate the heterogeneity with respect to psychopathology and IQ, and to use a global assessment scale (Children's Global Assessment Scale [CGAS]) to evaluate psychosocial functioning. Clinical neuropsychiatric and neuropsychological assessments were made at baseline and at the 2-year follow-up in 24 patients, and changes were analyzed at an individual level. Psychiatric disorders (mainly attention deficit hyperactivity disorder and/or autism spectrum disorders) were found in 17 of 24 at some point. All except one child with psychiatric diagnoses before surgery still had at least one diagnosis at follow-up. Intellectual ability remained stable in the majority of cases, both in individuals with and in individuals without mental retardation. The CGAS illustrated the consequences of the extensive comorbidity in this cohort. The behavioral problems had been undiagnosed despite parental concern in many cases, indicating an unrecognized need for services for children with drug-resistant epilepsy.
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| 22. |
- Danielsson, Susanna, 1964, et al.
(författare)
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Temporal Lobe Resections in Children with Epilepsy: Neuropsychiatric Status in Relation to Neuropathology and Seizure Outcome.
- 2002
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Ingår i: Epilepsy & behavior : E&B. - 1525-5069. ; 3:1, s. 76-81
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this work was to relate clinical neuropsychiatric findings to histopathological diagnoses and seizure outcome in a retrospective study of 16 children undergoing temporal lobe resections due to medically intractable epilepsy. These children constitute a heterogeneous group in which neuropsychiatric symptoms were common. The results of this study indicate a correlation between malformations of cortical development, less chance of seizure freedom, and neuropsychiatric problems in children with pharmacoresistant temporal lobe epilepsy. It is important to include neuropsychiatric assessments pre- and postoperatively and to inform parents that symptoms of autism spectrum disorders may or may not be improved after epilepsy surgery.
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| 23. |
- Eberhardson, Michael, et al.
(författare)
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Tumour necrosis factor inhibitors in Crohn's disease and the effect on surgery rates
- 2022
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Ingår i: Colorectal Disease. - : Wiley. - 1462-8910 .- 1463-1318. ; 24:4, s. 470-483
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Surgery is an important therapeutic option for Crohn's disease. The need for first bowel surgery seems to have decreased with the introduction of tumour necrosis factor inhibitors (TNFi; adalimumab or infliximab). However, the impact of TNFi on the need for intestinal surgery in Crohn's disease patients irrespective of prior bowel resection is not known. The aim of this work is to compare the incidence of bowel surgery in Crohn's disease patients who remain on TNFi treatment versus those who discontinue it. Method: We performed a nationwide register-based observational cohort study in Sweden of all incident and prevalent cases of Crohn's disease who started first-line TNFi treatment between 2006 and 2017. Patients were categorized according to TNFi treatment retention less than or beyond 1 year. The study cohort was evaluated with regard to incidence of bowel surgery from 12 months after the first ever TNFi dispensation. Results: We identified 5003 Crohn's disease patients with TNFi exposure: 3748 surgery naïve and 1255 with bowel surgery prior to TNFi initiation. Of these patients, 7% (n = 353) were subjected to abdominal surgery during the first 12 months after the start of TNFi and were subsequently excluded from the main analysis. A majority (62%) continued TNFi for 12 months or more. Treatment with TNFi for less than 12 months was associated with a significantly higher surgery rate compared with patients who continued on TNFi for 12 months or more (hazard ratio 1.26, 95% CI 1.09–1.46; p = 0.002). Conclusion: Treatment with TNFi for less than 12 months was associated with a higher risk of bowel surgery in Crohn's disease patients compared with those who continued TNFi for 12 months or more.
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| 24. |
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| 25. |
- Fjæstad, Björn, 1943-, et al.
(författare)
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National profile: Sweden
- 1998
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Ingår i: Biotechnology in the public sphere. - London : Science Museum. - 190074709X ; , s. 130-143
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 26. |
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| 27. |
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| 28. |
- Govender, Rydvikha, 1989, et al.
(författare)
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Enabling modular dosage form concepts for individualized multidrug therapy: Expanding the design window for poorly water-soluble drugs
- 2021
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Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 602
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Tidskriftsartikel (refereegranskat)abstract
- Multidrug dosage forms (aka combination dosage forms, polypills, etc.) create value for patients through reduced pill burdens and simplified administration to improve adherence to therapy. Enhanced flexibility of multidrug dosage forms would provide further opportunities to better match emerging needs for individualized therapy. Through modular dosage form concepts, one approach to satisfy these needs is to adapt multidrug dosage forms to a wider variety of drugs, each with a variety of doses and release profiles. This study investigates and technically explores design requirements for extending the capability of modular multidrug dosage form concepts towards individualization. This builds on our recent demonstration of independent tailoring of dose and drug release, which is here extended towards poorly water-soluble drugs. The challenging design requirement of carrying higher drug loads in smaller volumes to accommodate multiple drugs at their clinical dose is here met regarding dose and release performance. With a modular concept, we demonstrate high precision (<5% RSD) in dose and release performance of individual modules containing felodipine or naproxen in Kollidon VA64 at both a wide drug loading range (5% w/w and 50% w/w drug) and a small module size (3.6 mg). In a forward-looking design-based discussion, further requirements are addressed, emphasizing that reproducible individual module performance is predictive of dosage form performance, provided the modules are designed to act independently. Therefore, efforts to incorporate progressively higher drug loads within progressively smaller module volumes will be crucial to extend the design window further towards full flexibility of future dosage forms for individualized multidrug therapy.
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| 29. |
- Jacobson, Jan, et al.
(författare)
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Final testing protocols
- 2011
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This report is the final document summarizing the inspection and testing protocols of the eVALUE project. It describes principles, inspection protocols and testing protocols for performance testing of ICT-based safety systems. The inspection protocols (published earlier in D2.2) and the testing protocols introduced in D3.1 are replaced by the ones in D3.2. The older versions are obsolete and should be disregarded. The inspection protocols cover the definition of the test vehicle, HMI aspects, environmental conditions, and functional safety. The inspection protocols are used to prepare for the physical tests as well as evaluating the performance of the vehicle. The testing protocols address longitudinal, lateral, and stability-oriented traffic scenarios. The longitudinal scenarios include a pedestrian crossing the road in front of the vehicle, or the situation where a driver approaches a stationary queue of cars. Involuntarily lane departures and cars in the blind spot during a lane change are situations covered by the lateral scenarios. Exiting a highway, avoiding an obstacle, and braking on a partially ice-covered road surface are examples of traffic scenarios related to stability.
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| 30. |
- Kettunen, Petronella, et al.
(författare)
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Genetic Variants of GSK3B are Associated with Biomarkers for Alzheimer's Disease and Cognitive Function
- 2015
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Ingår i: Journal of Alzheimers Disease. - 1387-2877. ; 44:4, s. 1313-1322
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Tidskriftsartikel (refereegranskat)abstract
- Background: Glycogen synthase kinase 3 beta (GSK3B) is the major kinase phosphorylating tau protein. Hyperphosphorylated tau is one of the hallmarks of Alzheimer's disease (AD). Despite extensive research, the role of GSK3B in AD pathogenesis is not fully understood.Objective: To evaluate possible associations between gene variants of GSK3B and risk of AD. Methods: Twelve GSK3B tag single-nucleotide polymorphisms (SNPs), together with the previously AD-associated rs334558, were analyzed in 583 AD patients and 673 controls. Analyses on single marker and haplotype levels were done to relate to risk of AD, Mini-Mental State Examination (MMSE) scores, and cerebrospinal fluid (CSF) biomarker levels of total tau (T-tau), hyperphosphorylated tau (P-tau(181)), and amyloid-beta (A beta(42)).Results: After correction for multiple testing, we found a number of associations of gene variants with CSF biomarker levels and cognitive function in the AD patients. Firstly, rs334558 was associated with elevated T-tau levels (p(c) = 0.04). Next, rs1154597 showed association with reducedA beta(42) levels (pc = 0.007). Lastly, rs3107669was associated with lower MMSE scores (p(c) = 0.03). In addition, one more SNP was nominally significantly associated with reduced A beta(42) levels and another was associated with reduced MMSE.Conclusion: We found GSK3B gene variants associated with cognitive function and CSF biomarkers T-tau and A beta(42). To our knowledge, this is the first time GSK3B has been associated with cognitive function or CSF biomarkers reflecting neuronal degeneration (T-tau) and brain amyloid load (A beta(42)). The regulation of GSK3B needs to be investigated further, to fully understand how these GSK3B gene variants are involved in AD pathogenesis.
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| 31. |
- Kotronia, Antonia, et al.
(författare)
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Culture of engagement : Students as change agents before, during and after an examination-focused partnership
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Students can influence their education through evaluations and as representatives in university decision bodies. A way to give them more power is through participation in course development as equal partners. In this study, the relationship between the outcome of a student-teacher partnership and a culture of student influence and engagement is explored. This is done through specifically targeting examination, an area where formal power rests far away from the actual partnership. The partnership outcome was evaluated through post-project surveys and group interviews, together with post-course evaluations. The students in the project, most of them with significant experience as student representatives, emphasized their ability to make meaningful change. At the same time, the students taking the revised course appreciated the implemented changes. A culture of engagement positively affects the outcome of the partnership, while the partnership itself strengthens students in their roles as change agents.
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| 32. |
- Kreida*, Stefan, et al.
(författare)
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Protein-protein interactions in AQP regulation - biophysical characterization of AQP0-CaM and AQP2-LIP5 complex formation
- 2018
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Ingår i: Faraday Discussions. - : Royal Society of Chemistry (RSC). - 1359-6640 .- 1364-5498. ; 209:35, s. 35-54
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Tidskriftsartikel (refereegranskat)abstract
- Protein-protein interactions play important roles in regulating human aquaporins (AQP) by gating as well as trafficking. While structural and functional studies have provided detailed knowledge of AQP transport mechanisms, selectivity as well as gating by conformational changes of loops or termini, the mechanism behind how protein-protein interactions control AQP-mediated water transport through cellular membranes remains poorly characterized. Here we explore the interaction between two human AQPs and regulatory proteins: the interaction between AQP0 and calmodulin, which mediates AQP0 gating, as well as the interaction between AQP2 and LIP5, which is involved in trafficking. Using microscale thermophoresis (MST) and fluorescence anisotropy, two methods that have the advantage of low sample consumption and detergent compatibility, we show that the interactions can be studied using both full-length AQPs and AQP peptides corresponding to the regulatory protein binding sites. However, full-length AQPs gave better reproducibility between methods and for the first time revealed that AQP0 binds CaM in a cooperative manner, which was not seen in experiments using peptides. Our study highlights that, while peptides are great tools for locating binding sites and pinpointing interacting residues, full-length proteins may give additional insights, such as binding mechanism, allostery and cooperativity, important parameters for understanding protein-protein mediated regulation in the cellular context. Our work provides a platform for further studies of AQP regulation that may be of interest for designing drugs that target AQP complexes as well as the development of artificial bio-mimetic water channels for water-purification purposes.
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| 33. |
- Källbom, Susanna, et al.
(författare)
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Vacuum formed bio-based composite materials using polyolefin and thermally modified wood powder
- 2022
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Ingår i: Journal of Applied Polymer Science. - : Wiley. - 0021-8995 .- 1097-4628. ; 139:29
-
Tidskriftsartikel (refereegranskat)abstract
- For climate and sustainability reasons, there is an interest and incentive to produce plastic and rubber products with increased content of a bio-based component, preferably existing as an industrial by-product, for example, wood powder/sawdust. There are many studies on the making of wood-plastic composites, but hitherto very few consider vacuum forming as a processing technique, especially considering a biofiller. Here, the properties of a vacuum formed composite with thermally modified wood powder (with reduced water uptake) and a very ductile polyolefin, was reported. Surprisingly, even at a 15 wt% filler content, the composite remained ductile (extensibility of ca. 30%). The water uptake increased with increasing content of wood powder, but was never more than 5%. The water sorption kinetics indicated that the wood powder did not form a percolated continuous path through the material for easy access to the water, which led to a low water diffusivity (ca. 2 × 10−10 cm2 s−1). The calorimetric data showed that the biofiller, overall, did not affect the melting and crystallization behavior of the polymer matrix, nor the observed glass transition temperature. To conclude, vacuum forming was shown to be a viable technique for composites with a very ductile/elastic matrix and stiff fillers.
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| 34. |
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| 35. |
- Larsson, Andreas, et al.
(författare)
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Collaborative Healthcare Innovation in Sweden
- 2012
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Ingår i: Sustainable Innovation. - New York : Springer. - 9781461420767 - 9781461420774 ; , s. 49-62
-
Bokkapitel (refereegranskat)abstract
- Abstract in UndeterminedThe medical technology (medtech) industry in Sweden is situated withina complex innovation ecosystem, in which various stakeholders from the public,private and academic sectors need to collaborate to meet demands on effective andeffi cient healthcare. Demographics are changing and those in need of healthcare arenot only larger in numbers than ever but they are also more knowledgeable anddemanding. Increasing innovative performance is crucial in both the private andpublic healthcare sectors, but bold steps forward need to be taken in light of stricterrules and regulations for how healthcare stakeholders should manage both theirinternal processes and the ways in which they interact with other stakeholders in thelarger innovation system. The traditional way in which medtech companies gainaccess to user needs, primarily working through a sales–purchasing relationshipwith the public healthcare sector, is outdated and needs to be replaced with anincreasingly collaborative and cocreative model of healthcare innovation.This chapter describes experiences and lessons learned from InnoPlant, a 3-year(2008–2011) action learning project involving three companies from the Swedishmedtech industry, two county/regional councils responsible for public healthcare,and four academic institutions—carried out within the framework of the SwedishProduct Innovation Engineering program (PIEp). The purpose of the project was toadvance the capability of stakeholders from the public, private, and academic sectorsto collaborate in the cocreation of healthcare innovations.
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| 36. |
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| 37. |
- Ludvigsson, Jonas F., 1969-, et al.
(författare)
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Swedish Inflammatory Bowel Disease Register (SWIBREG) : a nationwide quality register
- 2019
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Ingår i: Scandinavian Journal of Gastroenterology. - : Taylor & Francis. - 0036-5521 .- 1502-7708. ; 54:9, s. 1089-1101
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Forskningsöversikt (refereegranskat)abstract
- Background: Inflammatory bowel disease (IBD) is a chronic, inflammatory relapsing disease with increasing incidence. IBD research and long-term follow-up of patients have, however, been hampered by lack of detailed data on disease phenotype, patient-reported outcome measures, Physician Global Assessment, disease activity, and hospital-administered drugs.Aim: To review the Swedish IBD quality register (SWIBREG).Methods: Review of SWIBREG including questionnaire data from users and patients.Results: SWIBREG was launched in 2005, and as of April 2019, contains 46,400 patients with IBD (Crohn's disease: n = 15,705, ulcerative colitis: n = 21,540, IBD unclassified and other colitis (including e.g., microscopic colitis): n = 9155). Of these IBD patients, 7778 had been diagnosed in childhood (16.8%). Earlier research has shown that combining SWIBREG and the Swedish National Patient Register (NPR) yields a positive predictive value of 100% (95%CI = 95-100%) for having a diagnosis of IBD. Moreover, out of all patients in the NPR with a diagnosis of IBD plus either IBD-related surgery or immunomodulatory/biological treatment during the past 18 months, SWIBREG covers 59.0%. SWIBREG records not only information on conventional therapies but also on biological treatment, surgery, smoking, disease activity, patient-reported outcome measures (PROMs), and patient-experienced measures (PREMs). Data are presented through a graphical decision support system.Conclusion: SWIBREG benefits patients with IBD, and offers an ideal opportunity for healthcare personnel and researchers to examine disease phenotype and activity, PROMs/PREMs, and hospital-administered drugs in patients with IBD.
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| 38. |
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| 39. |
- Marcia, Håkansson Lindqvist, et al.
(författare)
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Supporting academic writing for extended education teacher students
- 2021
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Konferensbidrag (refereegranskat)abstract
- Extended education provides possibilities to compensate for gaps within traditional education, bridging school learning with learning in extended education. However, according to the Swedish Schools Inspectorate (2018), there are challenges, among others, in relation to learning environments, planning and focus on teaching and collaboration with schools (cf Boström & Augustsson, 2016; Klerfelt & Haglund, 2014). New teachers in extended education, who today are extended education teacher students, will play an important role in this work and will need both professional as well as academic skills such as writing to bridge these gaps. This paper explores how extended education teacher students in a Swedish university context reflect upon their academic writing skills. Extended education students in their second year of studies were asked to write a learning reflection (N=14) about their academic writing skills. Questions posed were about students’ previous writing skills, self-assessments of their writing skills and writing processes and what support they perceived that they needed to develop their writing skills. The learning reflections were analysed using qualitative and quantitative Content Analysis (Boréus & Bergström, 2017). The teacher students reported both positive and negative previous experiences of writing in general. Many students noted negative experiences of writing during previous school years. Other students described more positive experiences, or that they in their experience of writing had seen a shift in experiences, either during their schools years or at university. The students also provided reflections on their writing processes. These processes showed wide variation, from trying to find structure in a text to seeing writing a text as building a puzzle. Many students focused on the need for structure, to practice writing and more developed skills in the genre of academic writing as well as support in understanding this genre as well as strong support in this process. However, students also saw the importance of developing their academic writing and the need to acquire this skill for their future studies. For the teacher students in this study support in academic writing is needed. These findings are of importance for teacher students to understand different writing strategies and processes, which come about in the process of learning the skill of academic writing. Moreover, these findings are important for teacher educators who strive to support extended education teacher students in academic writing and provide insights in that general and more specific support students’ needs. Further, these finding may also be of interest for higher education institutions, which seek to support teacher students’ academic writing. How extended education teacher students’ skills in academic writing develop, and later professional writing, may be an important key in bridging the gaps between traditional school teaching in extended education and supporting pupils’ learning. ReferencesBoréus, K., & Bergström, G. (2017). Analyzing text and discourses. Eight approaches for the social sciences. London: SAGE.Boström, L., & Augustsson, G. (2016). Learning Environments in Swedish Leisure-time Centres: (In)equality , “Schooling”, and Lack of Independence. International Journal for Research on Extended Education, 4(1), 125-145.Klerfelt, A., & Haglund, B. (2014). Presentation of Research on School-Age Educare in Sweden. International Journal for Research on Extended Education, 2(1), 45-63.The Swedish Schools Inspectorate. (2018). Undervisning i fritidshemmet [Teaching in Leisure-time Centres]. Stockholm: The Swedish Schools Inspectorate.
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| 40. |
- Mesilov, Vitaly, et al.
(författare)
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Regeneration of sulfur-poisoned Cu-SSZ-13 catalysts : Copper speciation and catalytic performance evaluation
- 2021
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Ingår i: Applied Catalysis B. - : Elsevier BV. - 0926-3373 .- 1873-3883. ; 299
-
Tidskriftsartikel (refereegranskat)abstract
- Regeneration of a sulfur-poisoned Cu-SSZ-13 catalyst via a temperature ramp in an inert atmosphere with subsequent holding under oxidizing conditions at 500 degrees C restores significant activity for NOx conversion under standard, fast, and NO2-rich SCR conditions. The N2O selectivity of the regenerated catalyst is higher than for the fresh catalyst under NO2-rich SCR conditions at 280 degrees C, while the opposite was observed for the standard and fast SCR conditions. Analysis of copper speciation showed that sulfur-free Cu species have different conditiondependent behavior in the fresh and regenerated catalysts. Heating the poisoned catalyst in an oxidizing atmosphere transforms a portion of ammonium sulfates into stable metal sulfates, while heating under inert or reducing conditions leads to more effective desulfation without the formation of stable metal sulfates. Reducing conditions result in desulfation at lower temperatures compared to inert conditions. These results contribute to the further development of regeneration strategies for Cu-SSZ-13 catalysts.
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| 41. |
- Mårild, Karl, 1982, et al.
(författare)
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Histologic activity in inflammatory bowel disease and risk of serious infections : A nationwide study
- 2024
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Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 22:4, s. 831-846
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Individuals with inflammatory bowel disease (IBD) are at increased risk of serious infections, but whether this risk varies by histological disease activity is unclear.METHODS: A national population-based study of 55,626 individuals diagnosed with IBD in 1990-2016 with longitudinal data on ileo-colorectal biopsies followed through 2016. Serious infections were defined as having an inpatient infectious disease diagnosis in the Swedish National Patient Register. We used Cox regression to estimate hazard ratios (HRs) for serious infections in the 12 months following documentation of histologic inflammation (vs. histological remission), adjusting for social and demographic factors, chronic comorbidities, prior IBD-related surgery and hospitalization. We also adjusted for IBD-related medications in sensitivity analyses.RESULTS: With histological inflammation vs. remission, there was 4.62 (95%CI=4.46-4.78) and 2.53 (95%CI=2.36-2.70) serious infections per 100 person-years of follow-up, respectively (adjusted [a]HR=1.59; 95%CI=1.48-1.72). Histological inflammation (vs. remission) were associated with an increased risk of serious infections in ulcerative colitis (UC, aHR=1.68; 95%CI=1.51-1.87) and Crohn's disease (CD, aHR=1.59; 95%CI=1.40-1.80). The aHRs of sepsis and opportunistic infections were 1.66 (95%CI=1.28-2.15) and 1.71 (95%CI=1.22-2.41), respectively. Overall, results were consistent across age groups, sex and education level and remained largely unchanged after adjustment for IBD-related medications (aHR=1.47; 95%CI=1.34-1.61).CONCLUSION: Histological inflammation of IBD was an independent risk factor of serious infections, including sepsis, suggesting that achieving histological remission may reduce infections in IBD.
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| 42. |
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| 43. |
- Olofsson, Sven-Olof, 1947, et al.
(författare)
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The formation of lipid droplets: possible role in the development of insulin resistance/type 2 diabetes.
- 2011
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Ingår i: Prostaglandins, leukotrienes, and essential fatty acids. - : Elsevier BV. - 1532-2823 .- 0952-3278. ; 85:5, s. 215-8
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Tidskriftsartikel (refereegranskat)abstract
- Neutral lipids are stored in so-called lipid droplets, which are formed as small primordial droplets at microsomal membranes and increase in size by a fusion process. The fusion is catalyzed by the SNARE proteins SNAP23, syntaxin-5 and VAMP4. SNAP23 is involved in the insulin dependent translocation of GLUT4 to the plasma membrane, and has an important role in the development of insulin resistance. Thus fatty acids relocalize SNAP23 from the plasma membrane (and the translocation of GLUT 4) to the interior of the cell giving rise to insulin resistance. Moreover this relocalization is seen in skeletal muscles biopsies from patients with type 2 diabetes compared to matched control. Thus a missorting of SNAP23 is essential for the development of insulin resistance.
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| 44. |
- Olsson, Ann-Margreth E., et al.
(författare)
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To Be Summoned to Barnahus: Children's Perspectives
- 2017
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Ingår i: Collaborating Against Child Abuse : Exploring the Nordic Barnahus Model - Exploring the Nordic Barnahus Model. - Lund : Palgrave Macmillan. - 9783319583877 - 9783319583884 ; , s. 57-74, s. 57-74
-
Bokkapitel (refereegranskat)abstract
- This chapter presents and analyses children’s narratives about being summoned to, arriving at and visiting a Barnahus. The children felt welcomed as guests, but hard work awaited them in the police investigative interview in front of frightening cameras and with strangers watching in an adjacent room. The children found that they needed more information about what was going on and why. From the children’s perspective, Barnahus became a house where children meet the police in serious matters. This chapter concludes with suggestions for further research and reflections for practitioners in consideration of children’s experiences of procedures and of being addressed as non-acting objects—instead of the acting subjects, the children talked about themselves as being, and acted as, in the research interviews.
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| 45. |
- Olsson, Erika, 1970-
(författare)
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Diet and common neurological disorders: cohort studies on dementia, Parkinson’s disease, and stroke
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Risk factors for dementia, Parkinson’s disease, and stroke have been widely studied but there are still research gaps concerning the role of diet for the development of these diseases. The overall aim of this thesis was to investigate whether various aspects of diet are associated with common disorders and diseases in the brain. Paper I and II are based on the Uppsala Longitudinal Study of Adult Men (ULSAM). Paper III and IV are based on the Swedish Mammography Cohort (SMC) and the Cohort of Swedish Men (COSM). In paper I, we investigated the associations between three different dietary patterns and incidence of Alzheimer’s disease (AD), dementia, and cognitive impairment. We observed no associations between adherence to the Healthy Diet Indicator and any of the outcomes studied, or between adherence to a Mediterranean-like diet (mMDS) and AD or dementia. There was a tendency towards a lower risk of cognitive impairment with higher adherence to the mMDS, and a weak association between adherence to a Low Carbohydrate High Protein score and higher risk of all-type dementia. Overall, there were no strong associations with the studied dietary patterns and development of dementia or cognitive impairment. In paper II, we found no associations of vitamin D measured as vitamin D intake, plasma 25-hydroxyvitamin D concentrations, or a vitamin D synthesis genetic risk score with incident AD, vascular dementia, dementia, or performance in the Mini-Mental State Examination.In paper III, we observed a weak higher risk of PD associated with milk consumption but there was no dose-response relationship. Thus, this association needs to be interpreted with caution. Fermented milk intake was not associated with PD.In paper IV, we found that a higher long-term milk consumption based on repeated measures of intake was not associated with total stroke, weakly and non-linearly associated with lower risk of cerebral infarction and higher risk of hemorrhagic stroke. Fermented milk consumption was not associated with any stroke type. Our results highlight the importance of repeated measurements of food intake, separate analyses of milk and fermented milk consumption, and to study stroke types separately.Despite the lack of strong associations, the findings of this thesis have increased our knowledge about the potential role of overall diet, vitamin D, and milk and fermented consumption in the prevention or development of common neurodegenerative diseases and stroke.
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| 46. |
- Olsson, Erika, 1970-, et al.
(författare)
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Milk and Fermented Milk Consumption and Risk of Stroke : Longitudinal Study
- 2022
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 14:5
-
Tidskriftsartikel (refereegranskat)abstract
- The role of milk and fermented milk consumption in stroke risk is unclear. We investigated associations of time-updated information on milk and fermented milk consumption (1997 and 2009) with total stroke, cerebral infarction, and hemorrhagic stroke risk among 79,618 Swedish women and men (mean age 61.3 years). During a mean follow-up of 17.7 years, we identified 9735 incident cases of total stroke, of which 7573 were cerebral infarctions, 1470 hemorrhagic strokes, and 692 unspecified strokes. Compared with an intake of 100 g/day of milk, the multivariable-adjusted hazard ratios (95% confidence interval) of cerebral infarction were 1.05 (1.02-1.08) for 0 g/day, 0.97 (0.95-0.99) for 200 g/day, 0.96 (0.92-1.00) for 400 g/day, 0.98 (0.94-1.03) for 600 g/day, and 1.01 (0.94-1.07) for 800 g/day. Corresponding estimates for hemorrhagic stroke were 0.98 (0.91-1.05) for 0 g/day, 1.02 (0.97-1.07) for 200 g/day, 1.07 (0.98-1.17) for 400 g/day, 1.13 (1.02-1.25) for 600 g/day, and 1.19 (1.03-1.36) for 800 g/day. No associations were observed between milk consumption and total stroke or for fermented milk consumption and any of the stroke outcomes. Higher long-term milk consumption based on repeated measures of intake was weakly and non-linearly associated with cerebral infarction, and was directly associated with hemorrhagic stroke.
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| 47. |
- Olsson, Erika, et al.
(författare)
-
Milk and Fermented Milk Intake and Parkinson's Disease : Cohort Study
- 2020
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Ingår i: Nutrients. - : MDPI. - 2072-6643. ; 12:9
-
Tidskriftsartikel (refereegranskat)abstract
- Milk and fermented milk consumption has been linked to health and mortality but the association with Parkinson's disease (PD) is uncertain. We conducted a study to investigate whether milk and fermented milk intakes are associated with incident PD. This cohort study included 81,915 Swedish adults (with a mean age of 62 years) who completed a questionnaire, including questions about milk and fermented milk (soured milk and yogurt) intake, in 1997. PD cases were identified through linkage with the Swedish National Patient and Cause of Death Registers. Multivariable-adjusted hazard ratios were obtained from Cox proportional hazards regression models. During a mean follow-up of 14.9 years, 1251 PD cases were identified in the cohort. Compared with no or low milk consumption (<40 mL/day), the hazard ratios of PD across quintiles of milk intake were 1.29 (95% CI 1.07, 1.56) for 40-159 mL/day, 1.19 (95% CI 0.99, 1.42) for 160-200 mL/day, 1.29 (95% CI 1.08, 1.53) for 201-400 mL/day, and 1.14 (95% CI 0.93, 1.40) for >400 mL/day. Fermented milk intake was not associated with PD. We found a weak association between milk intake and increased risk of PD but no dose-response relationship. Fermented milk intake was not associated with increased risk of PD.
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| 48. |
- Olsson, Ingrid, 1948, et al.
(författare)
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Epilepsy surgery in children with accompanying impairments.
- 2013
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Ingår i: European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society. - : Elsevier BV. - 1532-2130. ; 17:6, s. 645-650
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to assess seizure outcome 2 years after epilepsy surgery in a consecutive series of paediatric patients, with special focus on children with learning disabilities and other neuroimpairments in addition to the epilepsy. Outcome 2 years after surgery was assessed in 110 of 125 children operated upon for drug resistant epilepsy in Gothenburg 1987-2006. More than half of the children had learning disabilities, 43% motor impairments and 30% a neuropsychiatric diagnosis. Fifty-six per cent of those with an IQ<70 became seizure-free or had a >75% reduction in seizure frequency, and two thirds if the operation was a resection. The corresponding figure in those with more than 100 seizures per month was 15 out of 31, and another seven had a 50-75% reduction in seizure frequency. The message is that learning disability, motor impairment and psychiatric morbidity should not be contraindications for paediatric epilepsy surgery. More than half of the children with learning disabilities had a worthwhile seizure outcome, with even better results after resective surgery. Children with drug resistant epilepsy and additional severe neurological impairments should have the benefit of referral to a tertiary centre for evaluation for epilepsy surgery.
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| 49. |
- Olsson, Martina, 1996, et al.
(författare)
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Multiscale X-ray imaging and characterisation of pharmaceutical dosage forms
- 2023
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Ingår i: International Journal of Pharmaceutics. - 0378-5173 .- 1873-3476. ; 642
-
Tidskriftsartikel (refereegranskat)abstract
- A correlative, multiscale imaging methodology for visualising and quantifying the morphology of solid dosage forms by combining ptychographic X-ray computed nanotomography (PXCT) and scanning small- and wide-angle X-ray scattering (S/WAXS) is presented. The methodology presents a workflow for multiscale analysis, where structures are characterised from the nanometre to millimetre regime. Here, the method is demonstrated by characterising a hot-melt extruded, partly crystalline, solid dispersion of carbamazepine in ethyl cellulose. Characterisation of the morphology and solid-state phase of the drug in solid dosage forms is central as this affects the performance of the final formulation. The 3D morphology was visualised at a resolution of 80 nm over an extended volume through PXCT, revealing an oriented structure of crystalline drug domains aligned in the direction of extrusion. Scanning S/WAXS showed that the nanostructure is similar over the cross section of the extruded filament, with minor radial changes in domain sizes and degree of orientation. The polymorphic forms of carbamazepine were qualified with WAXS, showing a heterogeneous distribution of the metastable forms I and II. This demonstrates the methodology for multiscale structural characterization and imaging to enable a better understanding of the relationships between morphology, performance, and processing conditions of solid dosage forms.
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| 50. |
- Olsson, Susanna
(författare)
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A study of allergens in the mite Lepidoglyphus destructor, using monoclonal antibodies and recombinant techniques
- 1998
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Mites are one of the most common causes of allergic reactions in many parts of the world. They can broadly be divided into two categories: house dust mites, primarily found in dwellings, and storage mites, primarily found in farming environments and grain storage facilities. Storage mites have now also been shown to exist in house dust. Lepidoglyphus destructor (L. destructor) is one of the predominant storage mite species in Europe. This thesis focuses on the characterization of allergens in this mite species with emphasis on the major allergen Lep d 2, previously called Lep d 1. Several monoclonal antibodies (Mabs) were produced against L. destructor. One Mab, 117179, identified a new allergen complex with molecular weights of 79/93 kDa and over 60 % IgE reactivity, indicating that it could be of clinical importance. A second Mab, I 112138, reacted to the major allergen, Lep d 1 (now Lep d 2). The two Mabs were applied for histochemical staining of cut mite sections in combination with confocal laser scanning microscopy in order to localize the two allergens. They were found to be distributed differently in the mite body. The 79/93 kDa allergens were located quite distinctly to the cytoskeleton and were not present in faecal particles while Lep d I showed a widespread distribution around the gut and front regions of the mite as well as in the faecal particles. This indicates differences in biological functions, where the 79/93 kDa allergens might be structural components and Lep d 1 could be involved in digestion. To further characterize Lep d 1, cDNA cloning was performed, revealing a 125 amino acid protein with a 16 amino acid leader sequence. Polymorphism was shown to be present in this allergen and two isoforms were cloned, differing in 13 amino acid positions. The cDNA sequences revealed over 50% homology with the group 2 allergens from the Dermatophagoides mite species leading to the redesignation of Lep d I to Lep d 2. The two isoforms of Lep d 2 were then expressed as recombinant allergens in two different expression systems, the prokaryotic E. coli system and the eukaryotic baculovirus system. Both systems were shown to produce recombinant allergens with IgE reactivities comparable to that of native Lep d 2 and no apparent differences were shown in reactivity between the two isoforms. Also the production yields were similar, leading to the conclusion that these systems are equally efficient in producing recombinant Lep d 2. In the E. coli system recombinant mutants of Lep d 2 were produced using site directed mutagenesis. In these mutants we disrupted disulphide bonds in order to study the implications for IgE reactivity. We found that the bond formed between cysteines 72 and 77 in Lep d 2 is most important for IgE reactivity in this allergen, however, in order to significantly reduce immunogenicity a mutant with all the disulphide bonds had to be produced. This mutant (Lep d 2.6Cys) showed an approximate 100-fold reduction in IgE reactivity but had retained T cell reactivity. In conclusion, monoclonal antibodies and recombinant allergens have been shown useful in the characterization of L. destructor allergens. Moreover, recombinant Lep d 2 and the mutant variant are likely to contribute to improved diagnosis and treatment of L. destructor allergy.
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