| 1. |
- Lundgren, Markus, et al.
(författare)
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Analgesic antipyretic use among young children in the TEDDY study : No association with islet autoimmunity
- 2017
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Ingår i: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The use of analgesic antipyretics (ANAP) in children have long been a matter of controversy. Data on their practical use on an individual level has, however, been scarce. There are indications of possible effects on glucose homeostasis and immune function related to the use of ANAP. The aim of this study was to analyze patterns of analgesic antipyretic use across the clinical centers of The Environmental Determinants of Diabetes in the Young (TEDDY) prospective cohort study and test if ANAP use was a risk factor for islet autoimmunity. Methods: Data were collected for 8542 children in the first 2.5 years of life. Incidence was analyzed using logistic regression with country and first child status as independent variables. Holm's procedure was used to adjust for multiplicity of intercountry comparisons. Time to autoantibody seroconversion was analyzed using a Cox proportional hazards model with cumulative analgesic use as primary time dependent covariate of interest. For each categorization, a generalized estimating equation (GEE) approach was used. Results: Higher prevalence of ANAP use was found in the U.S. (95.7%) and Sweden (94.8%) compared to Finland (78.1%) and Germany (80.2%). First-born children were more commonly given acetaminophen (OR 1.26; 95% CI 1.07, 1.49; p = 0.007) but less commonly Non-Steroidal Anti-inflammatory Drugs (NSAID) (OR 0.86; 95% CI 0.78, 0.95; p = 0.002). Acetaminophen and NSAID use in the absence of fever and infection was more prevalent in the U.S. (40.4%; 26.3% of doses) compared to Sweden, Finland and Germany (p < 0.001). Acetaminophen or NSAID use before age 2.5 years did not predict development of islet autoimmunity by age 6 years (HR 1.02, 95% CI 0.99-1.09; p = 0.27). In a sub-analysis, acetaminophen use in children with fever weakly predicted development of islet autoimmunity by age 3 years (HR 1.05; 95% CI 1.01-1.09; p = 0.024). Conclusions: ANAP use in young children is not a risk factor for seroconversion by age 6 years. Use of ANAP is widespread in young children, and significantly higher in the U.S. compared to other study sites, where use is common also in absence of fever and infection.
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| 2. |
- Smith, Laura B., et al.
(författare)
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Psychological manifestations of celiac disease autoimmunity in young children
- 2017
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Ingår i: Pediatrics. - : American Academy of Pediatrics (AAP). - 0031-4005 .- 1098-4275. ; 139:3
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVES: Psychological symptoms can be associated with celiac disease; abstract however, this association has not been studied prospectively in a pediatric cohort. We examined mother report of psychological functioning in children persistently positive for tissue transglutaminase autoantibodies (tTGA), defined as celiac disease autoimmunity (CDA), compared with children without CDA in a screening population of genetically at-risk children. We also investigated differences in psychological symptoms based on mothers' awareness of their child's CDA status. METHODS: The Environmental Determinants of Diabetes in the Young study followed 8676 children to identify triggers of type 1 diabetes and celiac disease. Children were tested for tTGA beginning at 2 years of age. The Achenbach Child Behavior Checklist assessed child psychological functioning at 3.5 and 4.5 years of age. RESULTS: At 3.5 years, 66 mothers unaware their child had CDA reported more child anxiety and depression, aggressive behavior, and sleep problems than 3651 mothers of children without CDA (all Ps ≤ .03). Unaware-CDA mothers also reported more child anxiety and depression, withdrawn behavior, aggressive behavior, and sleep problems than 440 mothers aware of their child's CDA status (all Ps ≤.04). At 4.5 years, there were no differences. CONCLUSIONS: In 3.5-year-old children, CDA is associated with increased reports of child depression and anxiety, aggressive behavior, and sleep problems when mothers are unaware of their child's CDA status. Mothers' knowledge of their child's CDA status is associated with fewer reports of psychological symptoms, suggesting that awareness of the child's tTGA test results affects reporting of symptoms.
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| 3. |
- Törn, Carina, et al.
(författare)
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Complement gene variants in relation to autoantibodies to beta cell specific antigens and type 1 diabetes in the TEDDY Study
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- A total of 15 SNPs within complement genes and present on the ImmunoChip were analyzed in The Environmental Determinants of Diabetes in the Young (TEDDY) study. A total of 5474 subjects were followed from three months of age until islet autoimmunity (IA: n = 413) and the subsequent onset of type 1 diabetes (n = 115) for a median of 73 months (IQR 54-91). Three SNPs within ITGAM were nominally associated (p < 0.05) with IA: rs1143678 [Hazard ratio; HR 0.80; 95% CI 0.66-0.98; p = 0.032], rs1143683 [HR 0.80; 95% CI 0.65-0.98; p = 0.030] and rs4597342 [HR 1.16; 95% CI 1.01-1.32; p = 0.041]. When type 1 diabetes was the outcome, in DR3/4 subjects, there was nominal significance for two SNPs: rs17615 in CD21 [HR 1.52; 95% CI 1.05-2.20; p = 0.025] and rs4844573 in C4BPA [HR 0.63; 95% CI 0.43-0.92; p = 0.017]. Among DR4/4 subjects, rs2230199 in C3 was significantly associated [HR 3.20; 95% CI 1.75-5.85; p = 0.0002, uncorrected] a significance that withstood Bonferroni correction since it was less than 0.000833 (0.05/60) in the HLA-specific analyses. SNPs within the complement genes may contribute to IA, the first step to type 1 diabetes, with at least one SNP in C3 significantly associated with clinically diagnosed type 1 diabetes.
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| 4. |
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| 5. |
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| 6. |
- Balgård, Matts, et al.
(författare)
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Inclusion of pharmacy students in an interprofessional training ward placement for health care students in Sweden
- 2021
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- What was done?: Final year undergraduate pharmacy students, specialising clinical pharmacy,were given the opportunity to spend two weeks of their six months pharmacypractice to participate in an interprofessional training ward placement(ITWP) together with medical, nursing and physiotherapy students. During thistwo-week clinical placement, the students were collaboratively responsiblefor managing the care of geriatric inpatients while under supervision oflicensed practitioners.Why was it done?: ITWP for health care students is established at various teaching hospitals.However, to our knowledge, no such program in Scandinavia has includedpharmacy students. Clinical pharmacy is a growing profession in Sweden andother health care students will in the future work alongside with clinicalpharmacists. Therefore we set out to add pharmacy students to the ITWP team,believing that it would be a valuable experience for them to collaborate andshare knowledge with students from other health care professions. Equallyimportant, it is a way to promote the pharmacist’s competence andcontribution to the multiprofessional health care team, prior to graduation.How was it done?: A working group was formed consisting of teachers from the faculty ofpharmacy, a student representative and a working clinical pharmacist. Thegroup developed the initiative, including among other things, prerequisites,an evaluation plan, a workflow tool for clinical rounds and suggested tasksfor pharmacy students during the placement.What has been achieved?: The program has been running for three semesters and 6–8 pharmacy studentshave participated in the ITWP each semester. The initiative has beenevaluated using surveys. Participating pharmacy students expressed gainingnew knowledge and better insight into nursing care and the roles of the otherprofessions. Nursing students appreciated the support in medicationmanagement and medical students found the pharmacy students to be valuablediscussion partners that could challenge their drug-related decisions. Tutorsexpressed that the pharmacy students brought a beneficial dynamic to the ITWPteam.What next?: The opportunity for students from different professions to work together witha common objective in a real-life setting gives them valuable insight in eachother’s professional roles early in their careers. This good practiceinitiative could be used in other interprofessional training ward placementswishing to involve pharmacy students.
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| 7. |
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| 8. |
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| 9. |
- Bölke, Kristofer, et al.
(författare)
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Physical Modeling Study on the Mixing in the New IronArc Process
- 2018
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Ingår i: Steel Research International. - : WILEY-V C H VERLAG GMBH. - 1611-3683 .- 1869-344X. ; 89:7
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Tidskriftsartikel (refereegranskat)abstract
- IronArc is a newly developed technology for pig iron production with the aim to reduce the CO2 emission and energy consumption, compared to a conventional blast furnace route. In order to understand the fluid flow and stirring in the IronArc reactor, water modeling experiments are performed. Specifically, a down scaled acrylic plastic model of the IronArc pilot plant reactor is used to investigate the mixing phenomena and gas penetration depth in the liquid bath. The mixing time is determined by measuring the conductivity in the bath, after a sodium chloride solution is added. Moreover, the penetration depth is determined by analyzing the pictures obtained during the experimental process by using both a video camera and a high speed camera. The results show that the bath movements are strong and that a circular movement of the surface is present. The mixing in the model for the flow rate of 282 NLmin(-1) is fast. Specifically, the average mixing times are 7.6 and 10.2s for a 95% and a 99% homogenization degree, respectively. This is 15% and 18% (per degree of homogenization) faster compared to the case when using 3 gas inlets and the same flow rate.
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| 10. |
- Dalianis, Tina, et al.
(författare)
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Management of BK-virus infection - Swedish recommendations
- 2019
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Ingår i: Infectious Diseases. - : TAYLOR & FRANCIS LTD. - 2374-4235 .- 2374-4243. ; 51:7, s. 479-484
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Forskningsöversikt (refereegranskat)abstract
- BK-virus (BKV) associated nephropathy (BKVAN) and BKV associated haemorrhagic cystitis (HC) are complications of BKV infection/reactivation in renal and allogeneic haematopoietic stem cell transplantation (HSCT) patients, respectively. The task of how to manage these diseases was given to the chair by the Swedish Reference Group for Antiviral Therapy (RAV). After individual contributions by members of the working group, consensus discussions were held in a meeting on 23 January 2018 arranged by RAV. Thereafter, the recommendations were published in Swedish on November 2018. The current translation to English has been approved by all co-authors. High BKV serum levels suggest an increased risk for BKVAN and potential graft failure. For detection of BKVAN, careful monitoring of BKV DNA levels in serum or plasma is recommended the first year after renal transplantation and when increased creatinine serum levels of unknown cause are observed. Notably, a renal biopsy is mandatory for diagnosis. To reduce the risk for progression of BKVAN, there is no specific treatment, and tailored individual decrease of immunosuppression is recommended. For BKV-HC, BKV monitoring is not recommended, since BK-viruria frequently occurs in HSCT patients and the predictive value of BKV in plasma/serum has not been determined. However, the risk for BKV-HC is higher for patients undergoing myeloablative conditioning, having an unrelated, HLA-mismatched, or a cord blood donor, and awareness of the increased risk and early intervention may benefit the patients. Also for BKV-HC, no specific therapy is available. Symptomatic treatment, e.g. forced diuresis and analgesics could be of use.
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| 11. |
- Hede, Sanna-Maria, et al.
(författare)
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Oncoprotein stabilization in brain tumors
- 2014
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Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 0950-9232 .- 1476-5594. ; 33:39, s. 4709-4721
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Forskningsöversikt (refereegranskat)abstract
- Proteins involved in promoting cell proliferation and viability need to be timely expressed and carefully controlled for the proper development of the brain but also efficiently degraded in order to prevent cells from becoming brain cancer cells. A major pathway for targeted protein degradation in cells is the ubiquitin-proteasome system (UPS). Oncoproteins that drive tumor development and tumor maintenance are often deregulated and stabilized in malignant cells. This can occur when oncoproteins escape degradation by the UPS because of mutations in either the oncoprotein itself or in the UPS components responsible for recognition and ubiquitylation of the oncoprotein. As the pathogenic accumulation of an oncoprotein can lead to effectively sustained cell growth, viability and tumor progression, it is an indisputable target for cancer treatment. The most common types of malignant brain tumors in children and adults are medulloblastoma and glioma, respectively. Here, we review different ways of how deregulated proteolysis of oncoproteins involved in major signaling cancer pathways contributes to medulloblastoma and glioma development. We also describe means of targeting relevant oncoproteins in brain tumors with treatments affecting their stability or therapeutic strategies directed against the UPS itself.
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| 12. |
- Johansson, Patrik, et al.
(författare)
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A Patient-Derived Cell Atlas Informs Precision Targeting of Glioblastoma
- 2020
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 32:2
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Tidskriftsartikel (refereegranskat)abstract
- Glioblastoma (GBM) is a malignant brain tumor with few therapeutic options. The disease presents with a complex spectrum of genomic aberrations, but the pharmacological consequences of these aberrations are partly unknown. Here, we report an integrated pharmacogenomic analysis of 100 patient-derived GBM cell cultures from the human glioma cell culture (HGCC) cohort. Exploring 1,544 drugs, we find that GBM has two main pharmacological subgroups, marked by differential response to proteasome inhibitors and mutually exclusive aberrations in TP53 and CDKN2A/B. We confirm this trend in cell and in xenotransplantation models, and identify both Bcl-2 family inhibitors and p53 activators as potentiators of proteasome inhibitors in GBM cells, We can further predict the responses of individual cell cultures to several existing drug classes, presenting opportunities for drug repurposing and design of stratified trials. Our functionally profiled biobank provides a valuable resource for the discovery of new treatments for GBM.
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| 13. |
- Jönsson, Anna Maria, et al.
(författare)
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Reflections on Science–Stakeholder Interactions in Climate Change Adaptation Research within Swedish Forestry
- 2014
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Ingår i: Society & Natural Resources. - : Informa UK Limited. - 0894-1920 .- 1521-0723. ; 27:11, s. 1130-1144
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Tidskriftsartikel (refereegranskat)abstract
- Stakeholder engagement has become increasingly important in research programs focusing on climate change impact on ecosystem services. Communication between researchers and stakeholders, however, is often impaired by linguistic barriers, different priorities, and time constraints. This article examines the organizational aspects of science–stakeholder interactions, focusing on examples from the Swedish forestry sector. The study highlights the need articulated by the Swedish forestry sector for access to scientific knowledge, and we discuss how to present research findings in formats suitable to serve as decision support. Clear communication about common goals, expectations, resources, and time frames is needed in order to reduce the risk of stakeholder fatigue.
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| 14. |
- Kløcker Larsen, Rasmus, et al.
(författare)
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A framework for facilitating dialogue between policy planners and local climate change adaptation professionals : Cases from Sweden, Canada and Indonesia
- 2012
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Ingår i: Environmental Science and Policy. - : Elsevier BV. - 1462-9011 .- 1873-6416. ; 23, s. 12-23
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Tidskriftsartikel (refereegranskat)abstract
- The dominant approach to mainstreaming climate adaptation into sectoral policies relies on an ‘upscaling’ model in which it is envisaged to extract lessons from local change processes to inspire generic sub-national and national policies. One of the central methodological questions, which remain unanswered in climate change adaptation research, is exactly how public policy can learn from highly contextual experiences of community-based adaptation and what role should be played by case study research. In this paper we undertake a comparison between three large research projects in Sweden, Canada and Indonesia, which aim to study and/or foster local adaptation in selected case studies through a process of social learning. We present a novel framework based on mapping of ‘sense-making perspectives’, which enables analysis of the multiple ways case study research can support local climate adaptation and link such efforts to higher level public policy. The analysis demonstrates how methodological choices shape how case study research works at the interface between planned (steered/regulatory policy) and self-organised adaptation of stakeholders (non-coercive policy). In this regard, there is a need for a high degree of transparency from the research community to enable local professionals to decide on their stakes and interests when inviting researchers into their grounded activities. We conclude that case study research can achieve new significance if viewed as a platform to leverage stakeholder competencies when informing existing social structures and enable the implementation of political objectives, but equally driving the very reinvention and improvement of these institutions.
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| 15. |
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| 16. |
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| 17. |
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| 18. |
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| 19. |
- Mainwaring, Oliver, et al.
(författare)
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ARF suppression by MYC but not MYCN confers increased malignancy of aggressive pediatric brain tumors
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Medulloblastoma, the most common malignant pediatric brain tumor, often harbors MYC amplifications. Compared to high-grade gliomas, MYC-amplified medulloblastomas often show increased photoreceptor activity and arise in the presence of a functional ARF/p53 suppressor pathway. Here, we generate an immunocompetent transgenic mouse model with regulatable MYC that develop clonal tumors that molecularly resemble photoreceptor-positive Group 3 medulloblastoma. Compared to MYCN-expressing brain tumors driven from the same promoter, pronounced ARF silencing is present in our MYC-expressing model and in human medulloblastoma. While partial Arf suppression causes increased malignancy in MYCN-expressing tumors, complete Arf depletion promotes photoreceptor-negative high-grade glioma formation. Computational models and clinical data further identify drugs targeting MYC-driven tumors with a suppressed but functional ARF pathway. We show that the HSP90 inhibitor, Onalespib, significantly targets MYC-driven but not MYCN-driven tumors in an ARF-dependent manner. The treatment increases cell death in synergy with cisplatin and demonstrates potential for targeting MYC-driven medulloblastoma.
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| 20. |
- Makumbi Bugembe, Haq, et al.
(författare)
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Strengthening community structures for sustained ART provision in resource limited settings
- 2016
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: In Uganda there is a nationwide program to provide free antiretroviral treatment (ART). Despite this, the uptake of HIV care is still low in many of the rural areas. To address this, Rural Action Community Based Organisation (RACOBAO) in partnership with Pharmacists without Borders Sweden, funded by Forum Syd, implemented a project with the purpose of increasing uptake, retention and adherence to ART services. Description:The project targeted people living with HIV (PLHIV), from remote rural communities of Kinuuka, Mpumudde, and Kasagama in Lyantonde district in south western Uganda from January 2012 to December 2013. The main duty bearer was the district health office. Health workers at lower level units were trained as a prerequisite for accreditation of those units as static ART sites. PLHIVs identified and seconded volunteers that were trained as treatment helpers providing individual support to clients, including adherence counselling. They also formed a linkage between clients and health workers through quarterly interface meetings. In addition, PLHIV were mobilized into support groups for peer counselling and advocacy for ART services. Lessons Learned:The training of health workers led to the accreditation of three health centers as static ART sites. Since then, this innovative approach that begun in Lyantonde became a national policy and was rolled out nationally 2015. Uptake to care trippled from 1,350 in 2012 to 5,567 2014 and to 6,495 by December 2015. Retention to care among the targeted PLHIV increased to 92% by December 2015 way above the 80% national average. Treatment helpers bridged the gap for monitoring of PLHIV in their homes, a mandate of the government health workers. The advocacy platforms for PLHIV improved their visibility and their capacity to present their needs to duty bearers. These approaches spearheaded by RACOBAO formed a model that was successfully replicated in neighboring Sembabule district during 2014-2015. Conclusions/next step: Imbalances in the access and adherence to ART services are a function of structural and policy issues and this model aims at addressing both. It has successfully been implemented and evaluated in two rural districts in Uganda and can be replicated nationally to increase uptake, retention and adherence to ART services.
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| 21. |
- Plummer, Ryan, et al.
(författare)
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Flood Governance : A multiple country comparison of stakeholder perceptions and aspirations
- 2018
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Ingår i: Environmental Policy and Governance. - : Wiley. - 1756-932X .- 1756-9338. ; 28:2, s. 67-81
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Tidskriftsartikel (refereegranskat)abstract
- Flooding is routinely among the most disastrous annual events worldwide with extensive impacts on human wellbeing, economies and ecosystems. Thus, how decisions are made about floods (i.e. flood governance) is extremely important and evidence shows that it is changing, with non-governmental actors (civil society and the private sector) becoming involved in new and sometimes hybrid governance arrangements. This study investigates how stakeholders perceive floods to be governed and how they believe decision-making ought to occur, with the intent of determining to what extent changing governance is evident on the ground and how well (or poorly) it aligns with desired governance arrangements. Flood governance stakeholders were surveyed in five flood-prone geographical areas from Australia, Canada, Italy, the Netherlands and Sweden. The findings suggest that a reconfiguration of flood governance is underway with relatively little consensus regarding the specific arrangements and mechanisms in place during this transitionary period. Across the five cases, stakeholders indicated that they wanted flood governance to be organized at multiple levels, with strong government involvement and with diverse actor groups, and through mechanisms that match the involvement of these actors, with a lack of desirability for some specific configurations involving the private sector in particular. There was little alignment between stakeholder perceptions of governance currently in place and their desired arrangements, except for government involvement. Future research directions highlight the importance of the inclusion of stakeholder perspectives in assessing flood governance, and following the transition in flood governance over time.
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| 22. |
- Rystedt, Alma, et al.
(författare)
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Effect of Botulinum Toxin Concentration on Reduction in Sweating : a randomized, double-blind study
- 2013
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Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 0001-5555 .- 1651-2057. ; 93:6, s. 674-678
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Tidskriftsartikel (refereegranskat)abstract
- Dose-response studies of botulinum toxin for reduction of sweating are sparse in the literature. The aim of this study was to determine the most appropriate concentrations of Botox (R), Dysport (R), Xeomin (R) and NeuroBloc (R), respectively, in order to achieve the greatest reduction in sweating, thus reducing the costs and increasing the safety of treatment. Four concentrations of each product were investigated. Intradermal injections of all products and concentrations were applied to the backs of 20 consenting subjects, in a randomized, double-blind manner. Areas of anhidrotic and hypohidrotic skin were measured with an iodine-starch test after 4, 8 and 12 weeks, respectively. Optimal concentrations were found to be 25 U/ml for Botox and Xeomin, approximately 100 U/ml for Dysport, and 50 U/ml for NeuroBloc. When comparing the mean anhidrotic area per unit for 100 U/ml of each product, the calculated dose conversion ratios were 1:1.6:1.2:1.3 (Botox:Dysport:Xeomin:NeuroBloc). If, instead, the optimal concentration for each product was compared, the dose conversion ratios were 1:4.8:1.3:2.2. Thus, it is crucial to consider botulinum toxin concentration in a treatment regimen.
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| 23. |
- Swartling, Fredrik J., et al.
(författare)
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Cyclic GMP-dependent protein kinase II inhibits cell proliferation, Sox9 expression and Akt phosphorylation in human glioma cell lines
- 2009
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Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 0950-9232 .- 1476-5594. ; 28:35, s. 3121-3131
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Tidskriftsartikel (refereegranskat)abstract
- Earlier we used a glioma model to identify loci in the mouse genome, which were repeatedly targeted by platelet-derived growth factor (PDGF)-containing Moloney murine leukemia viruses. The gene Prkg2, encoding cyclic guanosine monophosphate (cGMP)-dependent protein kinase II, cGKII, was tagged by retroviral insertions in two brain tumors. The insertions were both situated upstream of the kinase domain and suggested creating a truncated form of the cGKII protein. We transfected different human glioma cell lines with Prkg2 and found an overall reduction in colony formation and cell proliferation compared with controls transfected with truncated Prkg2 (lacking the kinase domain) or empty vector. All glioma cells transfected with the cGKII phosphorylate vasodilator-stimulated phosphoprotein, VASP, after cGMP analog treatment. Glioma cell lines positive for the Sox9 transcription factor showed reduced Sox9 expression when Prkg2 was stably transfected. When cGKII was activated by cGMP analog treatment, Sox9 was phosphorylated, Sox9 protein expression was suppressed and the glioma cell lines displayed loss of cell adhesion, inhibition of Akt phosphorylation and G1 arrest. Sox9 repression by siRNA was similarly shown to reduce glioma cell proliferation. Expression analysis of stem and glial lineage cell markers also suggests that cGKII induces differentiation of glioma cell lines. These findings describe an anti-proliferative role of cGKII in human glioma biology and would further explain the retroviral tagging of the cGKII gene during brain tumor formation in PDGF-induced tumors.
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| 24. |
- Swartling, Fredrik J., 1975-, et al.
(författare)
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What underlies the diversity of brain tumors?
- 2013
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Ingår i: Cancer Metastasis Review. - : Springer. - 0167-7659 .- 1573-7233. ; 32:1-2 (SI), s. 5-24
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Forskningsöversikt (refereegranskat)abstract
- Glioma and medulloblastoma represent the most commonly occurring malignant brain tumors in adults and in children, respectively. Recent genomic and transcriptional approaches present a complex group of diseases and delineate a number of molecular subgroups within tumors that share a common histopathology. Differences in cells of origin, regional niches, developmental timing, and genetic events all contribute to this heterogeneity. In an attempt to recapitulate the diversity of brain tumors, an increasing array of genetically engineered mouse models (GEMMs) has been developed. These models often utilize promoters and genetic drivers from normal brain development and can provide insight into specific cells from which these tumors originate. GEMMs show promise in both developmental biology and developmental therapeutics. This review describes numerous murine brain tumor models in the context of normal brain development and the potential for these animals to impact brain tumor research.
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| 25. |
- Swartling, Maria, et al.
(författare)
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A Study of Dynamic Lining Temperature Variations in the Taphole Region of a Blast Furnace
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Ingår i: Steel Research International. - 1611-3683 .- 1869-344X.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The thermal behavior of the blast furnace hearth with special focus on the taphole regionwas studied. The original lining is in this region assumed to be replaced with tap clay,which influences the dynamic lining temperature variations. A heat transfer modelpreviously developed has been used to study the effect of the size and shape of the tapclay layer around the taphole. Four different cases have been calculated: one referencecase and three cases different tap clay layer geometries. It was found that the calculatedpeak-to-peak amplitudes of the lining temperatures during the tap cycles at the location ofa thermocouple can be approximated as a linear function of the tap clay layer thicknessesfor all calculated cases: the R2-value of the linear approximations were in the range 0.9-0.98. Modeling was also done where both the 90th and the 10th percentile of the observedpeak-to-peak values of the studied tap cycles were included to describe the behavior ofthe operating furnace. The calculation results show that the taphole region can be dividedinto three categories based on how well the model can describe the measured processdata: below, at and above taphole level. Below the taphole level, the measured liningtemperature variations are smaller than for the calculated results. At the taphole level, themodel can describe the behavior of the operating furnace. Above the taphole level, themeasured lining temperature variations are larger than for the calculated results. It wasconcluded, that in order to make a more accurate heat transfer model of the tapholeregion, the presence of a skull build-up below the taphole, erosion above the taphole andthe bath level variations need to be taken into account.
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| 26. |
- Swartling, Maria, 1983-
(författare)
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A Study of the Heat Flow in the Blast Furnace Hearth Lining
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of the present thesis was to study the heat flows in the blast furnace hearth lining by experimental measurements and numerical modeling. Thermocouple data from an operating furnace have been used throughout the work, to verify results and to develop methodologies to use the results in further studies. The hearth lining were divided into two zones based on the thermocouple readings: a region with regular temperature variations due to the tapping of the furnace, and another region with slow temperature variations. In an experimental study, the temperatures of the outer surfaces of the wall and bottom were measured and compared with lining temperature measured by thermocouples. Expressions to describe the outer surface temperature profiles were derived and used as input in a two-dimensional steady state heat transfer model. The aim of the study was to predict the lining temperature profiles in the region subjected to slow temperature variations. The methodology to calculate a steady state lining temperature profile was used as input to a three-dimensional model. The aim of the three-dimensional model was primarily to study the region with dynamic lining temperature variations caused by regular tappings. The study revealed that the replacement of original lining with tap clay has an effect when simulating the quasi-stationary temperature variations in the lining. The study initiated a more detailed study of the taphole region and the size and shape of the tap clay layer profile. It was concluded, that in order to make a more accurate heat transfer model of the blast furnace hearth, the presence of a skull build-up below the taphole, erosion above the taphole and the bath level variations must to be taken into consideration.
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| 27. |
- Swartling, Maria, 1983-
(författare)
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An Experimental and Numerical Study of the Heat Flow in the Blast Furnace Hearth
- 2008
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This study has focused on determining the heat flows in a production blast furnace hearth. This part of the blast furnace is exposed to high temperatures. In order to increase the campaign length of the lining an improved knowledge of heat flows are necessary. Thus, it has been studied both experimentally and numerically by heat transfer modeling. Measurements of outer surface temperatures in the lower part of a production blast furnace were carried out. In the experimental study, relations were established between lining temperatures and outer surface temperatures. These relations were used as boundary conditions in a mathematical model, in which the temperature profiles in the hearth lining are calculated. The predictions show that the corner between the wall and the bottom is the most sensitive part of the hearth. Furthermore, the predictions show that no studied part of the lining had an inner temperature higher than the critical temperature 1150°C, where the iron melt can be in contact with the lining.
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| 28. |
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| 29. |
- Swartling, Maria, et al.
(författare)
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Experimentally determined temperatures in blast furnace hearth
- 2010
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Ingår i: Ironmaking & steelmaking. - 0301-9233 .- 1743-2812. ; 37:1, s. 21-26
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Tidskriftsartikel (refereegranskat)abstract
- In this study temperature measurements have been carried out at blast furnace no. 2 at SSAB Oxelosund. The temperature was measured in the hearth lining and at the outer surfaces of the hearth wall and bottom. The lining temperature was measured using permanently installed thermocouples and surface temperatures were measured using a hand held thermocouple. The aims of the study were to find a correlation between lining and surface temperatures as well as to find a method to determine the surface temperature based on readings from lining thermocouples. The overall conclusion is that the bottom and wall surface temperatures can be determined based on lining temperatures.
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| 30. |
- Swartling, Maria, et al.
(författare)
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Heat Transfer Modelling of a Blast Furnace Hearth
- 2010
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Ingår i: STEEL RES INT. - : Wiley. - 1611-3683. ; 81:3, s. 186-196
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Tidskriftsartikel (refereegranskat)abstract
- This paper describes the development of a heat transfer model with the purpose of studying the heat flows in the hearth of an operating blast furnace. Temperature profiles were calculated for a period of time to study the transition from steady blast furnace operation to an unsteady period, and back to a steady period. This total time period had the highest lining temperatures registered since the beginning of the current campaign. It was concluded that no part of the lining had an inner temperature higher than the critical temperature of 1150 degrees C. Thus, no refractory could have been in direct contact with slag or iron. The corner between the wall and the bottom was identified to be the most sensitive part of the lining. It is suggested that thermocouples are installed in this area, to improve the temperature control.
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| 31. |
- Swartling, Maria, et al.
(författare)
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Heat Transfer Study of Blast Furnace 2 at SSAB Oxelösund
- 2009
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Ingår i: Journal of Iron and Steel Research International. - 1006-706X .- 2210-3988. ; 16:Part 2 Suppl. 2, s. 1131-1136, s. 1131-1136
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents a heat transfer study, based on the actual conditions of the hearth of Blast Furnace 2 at SSAB Oxelosund in Sweden. Initially, an experimental study was carried out. The temperature of the cold surfaces of the bottom and wall lining were measured with a hand-held thermocouple. The aim of the overall study was to find a method to determine the outer surface temperature, based on lining temperature readings from permanently installed thermocouples. A heat transfer model was developed, using the established correlations from the experimental study as boundary conditions. With the model, it is possible to calculate a complete two-dimensional temperature profile of the hearth lining at any given time. The permanently installed thermocouples are used to validate the model, by comparing calculated and measured temperatures; the accuracy of the model is plus/minus 3 degrees difference.
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| 32. |
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| 33. |
- Swartling, Maria, et al.
(författare)
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Interpretation of Tap Induced Cyclic Temperatures in the Blast Furnace Lining
- 2012
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Ingår i: Steel Research International. - : Wiley. - 1611-3683 .- 1869-344X. ; 83:7, s. 695-704
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Tidskriftsartikel (refereegranskat)abstract
- The thermal behavior of the blast furnace hearth was studied using modeling. The focus was the effect of the size and shape of the taphole clay layer around the taphole. Four different cases have been calculated: one reference case and three cases with different taphole clay layer geometries. It was found that the calculated peak-to-peak amplitudes of the lining temperatures during the tap cycles at the location of a thermocouple can be approximated as a linear function of the taphole clay layer thicknesses for all calculated cases. Modeling was also done where both the 90th and the 10th percentile of the observed peak-to-peak values of the studied tap cycles were included to describe the behavior of the operating furnace. The taphole region can be divided into three categories based on how well the model can describe the measured process data: below, at, and above taphole level. Below the taphole level, the measured lining temperature variations are smaller than for the calculated results. At the taphole level, the model can describe the behavior well. Above the taphole level the measured lining temperature variations are larger than for the calculated results. It was concluded that in order to make a more accurate heat transfer model of the taphole region, the presence of a skull build-up below the taphole, erosion above the taphole, and the bath level variations need to be taken into account.
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| 34. |
- Swartling, Maria
(författare)
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Klinisk praktik på sjukhus - Effektiv handledning av blivande kliniska farmaceuter
- 2011
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Klinisk praktik på sjukhus - Effektiv handledning av blivande kliniska farmaceuter Inledning:Institutionen för farmaceutisk biovetenskap ger två kurser i ämnet klinisk farmaci innefattande verksamhetsförlagd utbildning (VFU). Under VFU behövs handledning av professionellt verksamma personer. Eftersom det finns ett begränsat antal tillgängliga handledare, en begränsad budget och ett behov av kvalitativ undervisning av studenterna behöver det utvecklas metoder för att göra handledningen ekonomiskt hållbar, effektiv och högkvalitativ. En av kurserna kräver handledning i större grupp, den andra baseras på individuell handledning.Syfte:Projektet hade tre delmål; att öka kompetensen för lärare på institutionen i handledning av studenter, att utveckla kostnadseffektiva och högkvalitativa modeller för pedagogisk klinisk handledning samt att under en projektfas prova och utvärdera modellerna.Metod:Under vårterminen 2010 deltog en av kursernas huvudlärare i en handledningskurs vid avdelningen för universitetspedagogisk utveckling. Intervjuer genomfördes också med representanter för andra svenska vårdutbildningar samt utländska farmaceutiska utbildningar för att lära mer om deras handledningsmodeller. En aktivitetsplan utarbetades för handledningen på de två kurserna och under höstterminen 2010 testades och utvärderades denna.Resultat och diskussion:Handledning i grupp utformades via ett diskussionsforum på studentportalen. På forumet fick studenterna möjlighet att diskutera situationer de stött på under sin VFU med en yrkesverksam klinisk farmaceut. Genom att använda studentportalen kunde alla studenter delta i diskussionerna. För ytterligare reflektion kring arbetsuppgifter och yrkesroll förde studenterna en reflektiv dagbok fortlöpande under VFU. Denna används sedan som diskussionsunderlag vid ett seminarium.Även peer-learning infördes på kursen genom att peer-grupper bildades och uppmuntrades att träffas regelbundet under VFUn. De gav även varandra återkoppling på inlämningsuppgifter. Studenterna var generellt positiva till såväl handledning via diskussionsforum, reflektiv praktik samt peer-learning. Aktivitetsgraden på forumet har dock varierat. Studenterna uttryckte att de lär sig mycket av att återkoppla på varandras inlämningsuppgifter och lärarna noterade att kvaliteten på inlämningsuppgifterna har höjts. Det har varit en utmaning att effektivisera handledningen och höja kvaliteten på kursen med individuell klinisk handledning. Kursledningen tog över handledningen av inlämningsuppgifter för att säkerställa en jämn nivå på handledningen samt frigöra mer tid för klinisk handledning. Även på denna kurs infördes peer-learning på samma sätt. En handledarutbildning med fokus på teorier och metoder för handledning utarbetades och genomfördes första gången under projektfasen. För att ytterligare säkerställa kvaliteten utarbetades ett dokument med kvalitetskriterier för den kliniska handledaren. För att förbättra feedback från handledare till student under VFU utarbetades bedömningskriterier av studentens förmågor. Detta användes som diskussionsunderlag mellan studenten och den kliniska handledaren vid en nyinrättad halvtidskontroll och slutbedömning. Kursvärderingar visar att handledarutbildningen har fallit väldigt väl ut, handledarna som deltog är mycket positiva och studenternas uppfattning är att handledarna i större utsträckning nu än tidigare fokuserar på färdigheter och arbetssätt. Peer-learning som metod fungerade bra för de studenter som gjorde sin VFU i närheten av varandra och kunde träffas och mindre bra för övriga. Projektet har resulterat i en kvalitetshöjning på båda kurserna, en kostnadsminskning för individuell handledning samt en minskad arbetsbörda för de kliniska handledarna. Det gedigna bakgrundsarbetet med intervjuer var avgörande för utvecklandet av kurserna och det goda resultat.
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| 35. |
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| 36. |
- Swartling, Maria
(författare)
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OSCE som metod för examination efter verksamhetsförlagd utbildning inom klinisk farmaci
- 2016
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- OSCE (objective structured clinical examination) som metod för examination efter verksamhetsförlagd utbildning inom klinisk farmaciMaria Swartling och Elisabet Nielsen. Avd för farmaceutisk biovetenskap, Uppsala universitetIntroduktion: På magisterprogrammet i klinisk farmaci, som är en yrkesinriktad utbildning, finns kursmål för kliniska arbetsmetoder samt kommunikationsfärdigheter. För att examinera dessa mål används OSCE (objective structured clinical examination). OSCE presenterades 1975 (Harden et al) som en metod att utvärdera klinisk kompetens hos medicinstuderande på ett objektivt sätt. Sedan dess har metoden utvecklats och används också inom farmaciutbildningar med klinisk inriktning (Sturpe, 2010).Metod: Som förberedelse inför VFU (verksamhetsförlagd utbildning) får studenten öva på arbetsmetoder och kommunikation under workshops och under en övnings-OSCE som är upplagd på samma sätt som den examinerande OSCE:n. Därefter går studenten ut på VFU och använder där metoderna i verkliga situationer. Studenten handleds under VFU men handledaren har inte en examinerande roll.OSCE i klinisk farmaci bygger på ett patientfall där studenten först får genomföra en läkemedelsintervju hos en skådespelare som spelar patient. Därefter får studenten möta en person som spelar läkare i en rondsituation, lägga fram åtgärdsförslag och argumentera för dessa. Under båda dessa samtal sitter en bedömare med och bedömer arbetsmetoderna samt kommunikationen enligt i förväg bestämda bedömningskriterier som utgår från kursmålen. Resultat/Diskussion: Kursvärderingar visar att studenterna överlag uppskattar examinationsformen och att den ger en rättvisande bild av deras förmåga. Den kritik som framkommit rör framför allt att situationen är konstlad och inte liknar verkligheten. Patientsamtalet upplevs som mindre verklighetstroget än rondsituationen. De uppskattar möjligheten att få öva på OSCE-situationen en gång innan examination så att de vänjer sig vid formatet.Lärarna upplever att OSCE är en bra metod för att garantera att målen för färdigheter uppnås. Med hjälp av bedömningskriterierna kan man på ett transparent sätt underkänna studenter när så behövs och visa på vilka delar som brister. En utmaning med examinationsformen är att det är resurskrävande. Det ligger ett stort förberedelsejobb bakom varje OSCE och det involverar fyra personer som skådespelare/bedömare på examinationsdagen. Förberedelsearbetet underlättas av att engagera en lärare som arbetar i klinisk praktik, då riktiga patientfall kan användas som underlag.Genom att examinera VFU på ett objektivt sätt under samma förutsättningar för alla studenter säkerställs en rättvis och homogen bedömning. Ett alternativ kan vara att handledaren examinerar studenten under VFU, men då riskerar bedömningen att bli olika för olika studenter och risken för subjektivitet i bedömningen ökar. Ett annat alternativ kan vara att en examinator besöker studenterna under VFU och examinerar på plats, men då studenterna är placerade på olika platser i landet är detta inte praktiskt genomförbart i det här fallet.Slutsats: OSCE fungerar som en bra metod att examinera kliniska färdigheter och kommunikation för studenter inom klinisk farmaci. Den största kritiken från studenthåll är att situationen inte är helt verklighetstrogen. Att öva på OSCE vid ett tillfälle innan examination förbereder studenterna på ett bra sätt. Harden RM et al. Assessment of clinical competence using objective structured examination. BMJ 1975;1:447-451Sturpe DA. Objective structured clinical examinations in Doctor of Pharmacy programs in the United States. Am J Pharm Educ 2010;74:1-6
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| 37. |
- Swartling, Maria, et al.
(författare)
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Population pharmacokinetics of cefotaxime in intensive care patients
- 2022
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Ingår i: European Journal of Clinical Pharmacology. - : Springer Science and Business Media LLC. - 0031-6970 .- 1432-1041. ; 78:2, s. 251-258
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To characterise the pharmacokinetics and associated variability of cefotaxime in adult intensive care unit (ICU) patients and to assess the impact of patient covariates.METHODS: This work was based on data from cefotaxime-treated patients included in the ACCIS (Antibiotic Concentrations in Critical Ill ICU Patients in Sweden) study. Clinical data from 51 patients at seven different ICUs in Sweden, given cefotaxime (1000-3000 mg given 2-6 times daily), were collected from the first day of treatment for up to three consecutive days. In total, 263 cefotaxime samples were included in the population pharmacokinetic analysis.RESULTS: A two-compartment model with linear elimination, proportional residual error and inter-individual variability (IIV) on clearance and central volume of distribution best described the data. The typical individual was 64 years, with body weight at ICU admission of 92 kg and estimated creatinine clearance of 94 mL/min. The resulting typical value of clearance was 11.1 L/h, central volume of distribution 5.1 L, peripheral volume of distribution 18.2 L and inter-compartmental clearance 14.5 L/h. The estimated creatinine clearance proved to be a significant covariate on clearance (p < 0.001), reducing IIV from 68 to 49%.CONCLUSION: A population pharmacokinetic model was developed to describe cefotaxime pharmacokinetics and associated variability in adult ICU patients. The estimated creatinine clearance partly explained the IIV in cefotaxime clearance. However, the remaining unexplained IIV is high and suggests a need for dose individualisation using therapeutic drug monitoring where the developed model, after evaluation of predictive performance, may provide support.
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| 38. |
- Swartling, Maria, et al.
(författare)
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Short term impact of guidelines on vancomycin dosing and therapeutic drug monitoring
- 2012
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Ingår i: International Journal of Clinical Pharmacy. - : Springer Science and Business Media LLC. - 2210-7703 .- 2210-7711. ; 34:2, s. 282-285
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Tidskriftsartikel (refereegranskat)abstract
- Background: After medical center implementation of 2009 ASHP/IDSA guidelines, we evaluated the appropriateness of vancomycin dosing and TDM. Objective: Our primary objectives were to assess short term effects on (1) appropriateness of initial vancomycin dosing, (2) appropriateness of sampling of plasma levels, before and after implementation of guidelines. Method: The study was conducted in two phases, pre-guideline and post-guideline implementation. The interventions included (1) Nurses and phlebotomist education regarding the appropriate timing of vancomycin sampling, (2) A nomogram for appropriate initial dosing that was distributed to medical staff. Patient demographics, dosing and timing of sampling were collected in eligible patients and assessed for appropriateness. Results: The appropriateness of the prescribed dose increased from 51% (128/253) of patients during the pre period to 78% (155/200) (p < 0.0001) during the post period. Similarly, overall appropriateness of sampling of vancomycin troughs at steady state improved from 36% (63/173) pre to 55% (106/191) (p < 0.03) post. Specifically, the appropriate timing of troughs (within 30 min of the next dose) increased from 37% (64/173) during the pre period to 78% (149/191) during the post period (p < 0.0001). Conclusion: Adoption of the guidelines with associated training resulted in significant short term improvement in vancomycin dosing and TDM.
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| 39. |
- Swartling, Maria, et al.
(författare)
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Short-term Lining Temperature Changes during Tapping in a Blast Furnace
- 2010
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Ingår i: Steel Research International. - : Wiley. - 1611-3683. ; 81:9, s. 724-734
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Tidskriftsartikel (refereegranskat)abstract
- The following paper presents a three-dimensional heat transfer model of the blast furnace hearth. The model has been developed with the objective of studying the short term changes in lining temperature during regular tappings. It is based on the actual conditions of Blast Furnace No. 2 at SSAB Oxelosund in Sweden. The model was evaluated and analysed using thermocouple data from the operating furnace. The study showed that a layer of tap clay around the tap hole had a significant effect on the heat transfer by reducing the heat variations in the lining. More specifically, a layer of 10-15 cm gave the best correlation between calculated and thermocouple data. A simulation was performed where the melt temperature and the tap cycle duration was based on process data from the operating furnace. Moreover, the size of the area subjected to changes due to the regular tappings was defined. It was found to be the region within an angle of 13 degrees from the tap hole, 0.9 m above and 0.8 m below the tap hole.
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| 40. |
- Swartling, Maria, et al.
(författare)
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Therapeutic drug monitoring of vancomycin and meropenem : Illustration of the impact of inaccurate information in dose administration time
- 2023
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Ingår i: International Journal of Antimicrobial Agents. - : Elsevier. - 0924-8579 .- 1872-7913. ; 63:1
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To illustrate the impact of errors in documented dose administration time on therapeutic drug monitoring (TDM)-based target attainment evaluation for vancomycin and meropenem, and to explore the influence of drug and patient characteristics, and TDM sampling strategies.Methods: Bedside observations of errors in documented dose administration times were collected. Population pharmacokinetic simulations were performed for vancomycin and meropenem, evaluating different one- and two-sampling strategies for populations with estimated creatinine clearance (CLcr) of 30, 80 or 130 mL/min. The impact of errors was evaluated as the proportion of individuals incorrectly considered to have reached the target.Results: Of 143 observed dose administrations, 97% of doses were given within ±30 min of the documented time. For vancomycin, a +30 min error was predicted to result in a 0.1-3.9 percentage point increase of cases incorrectly evaluated as reaching area under the concentration-time curve during a 24-hour period (AUC24)/minimum inhibitory concentration (MIC) >400, with the largest increase for patients with augmented renal clearance and peak and trough sampling. For meropenem, a +30 min error resulted in a 1.3-6.4 and 0-20 percentage point increase of cases incorrectly evaluated as reaching 100% T>MIC, and 50% T>MIC, respectively. Overall, mid-dose and trough sampling was most favourable for both antibiotics.Conclusions: For vancomycin, simulations indicate that TDM-based target attainment evaluation is robust with respect to the observed errors in dose administration time of ±30 min; however, the errors had a potentially clinically important impact in patients with augmented renal clearance. For meropenem, extra measures to promote correct documentation are warranted when using TDM, as the impact of errors was evident even in patients with normal renal function.
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| 41. |
- Swartling, Oskar, et al.
(författare)
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CKD Progression and Mortality Among Men and Women : A Nationwide Study in Sweden
- 2021
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Ingår i: American Journal of Kidney Diseases. - : Elsevier BV. - 0272-6386. ; 78:2, s. 190-
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Tidskriftsartikel (refereegranskat)abstract
- Rationale & Objective: Chronic kidney disease (CKD) is a global health problem with increasing prevalence. Several sex-specific differences have been reported for disease progression and mortality. Selection and survival bias might have influenced the results of previous cohort studies. The objective of this study was to investigate sex-specific differences of CKD progression and mortality among patients with CKD not receiving maintenance dialysis. Study Design: Observational cohort study. Setting & Participants: Adult patients with incident CKD glomerular filtration rate categories 3b to 5 (G3b-G5) identified between 2010 and 2018 within the nationwide Swedish Renal Registry-CKD (SRR-CKD). Exposure: Sex. Outcomes: Time to CKD progression (defined as a change of at least 1 CKD stage or initiation of kidney replacement therapy [KRT]) or death. Repeated assessments of estimated glomerular filtration rate (eGFR). Analytical Approach: CKD progression and mortality before KRT were assessed by the cumulative incidence function methods and Fine and Gray models, with death handled as a competing event. Sex differences in eGFR slope were estimated using mixed effects linear regression models. Results: 7,388 patients with incident CKD G3b, 18,282 with incident CKD G4, and 9,410 with incident CKD G5 were identified. Overall, 19.6 (95% CI, 19.2-20.0) patients per 100 patient-years progressed, and 10.1 (95% CI, 9.9-10.3) patients per 100 person-years died. Women had a lower risk of CKD progression (subhazard ratio [SHR], 0.88 [95% CI, 0.85-0.92]), and a lower all-cause (SHR, 0.90 [95% CI, 0.85-0.94]) and cardiovascular (SHR, 0.83 [95% CI, 0.76-0.90]) mortality risk. Risk factors related to a steeper decline in eGFR included age, sex, albuminuria, and type of primary kidney disease. Limitations: Incomplete data for outpatient visits and laboratory measurements and regional differences in reporting. Conclusions: Compared to women, men had a higher rate of all-cause and cardiovascular mortality, an increased risk of CKD progression, and a steeper decline in eGFR.
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