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| 6. |
- Thalén, Niklas, 1985-, et al.
(författare)
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Systems biology greatly improve activity of secreted therapeutic sulfatase in CHO bioprocess
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Rare diseases are, despite their name, collectively common and millions of people are affected daily of conditions where treatment often is unavailable. Sulfatases are a large family of activating enzymes related to several of these diseases. Heritable genetic variations in sulfatases may lead to impaired activity and a reduced macromolecular breakdown within the lysosome, with several severe and lethal conditions as a consequence. While therapeutic options are scarce, treatment for some sulfatase deficiencies by recombinant enzyme replacement are available. However, such recombinant production of sulfatases suffers greatly from low product activity and yield, further limiting accessibility for patient groups. Here, we have addressed this problem by defining key-proteins necessary for active sulfatase secretion by comparison of CHO clones with different levels of production of active sulfatase. Quantitative transcriptomic analysis highlighted 14 key genes associated with sulfatase production, and experimental validation by co-expression improved the sulfatase enzyme activity by up to 150-fold. Furthermore, a correlation between product mRNA levels and sulfatase activity were observed and expression with lower activity promoters showed an increased in sulfatase activity. The workflow devised is general and we propose it to be useful for resolving bottlenecks in cellular machineries for improvement of cell factories for other biologics as well.
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| 7. |
- Thalén, Niklas, et al.
(författare)
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Tuning of CHO secretional machinery improve activity of secreted therapeutic sulfatase 150-fold
- 2024
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Ingår i: Metabolic engineering. - : Elsevier BV. - 1096-7176 .- 1096-7184. ; 81, s. 157-166
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Tidskriftsartikel (refereegranskat)abstract
- Rare diseases are, despite their name, collectively common and millions of people are affected daily of conditions where treatment often is unavailable. Sulfatases are a large family of activating enzymes related to several of these diseases. Heritable genetic variations in sulfatases may lead to impaired activity and a reduced macromolecular breakdown within the lysosome, with several severe and lethal conditions as a consequence. While therapeutic options are scarce, treatment for some sulfatase deficiencies by recombinant enzyme replacement are available. The recombinant production of such sulfatases suffers greatly from both low product activity and yield, further limiting accessibility for patient groups. To mitigate the low product activity, we have investigated cellular properties through computational evaluation of cultures with varying media conditions and comparison of two CHO clones with different levels of one active sulfatase variant. Transcriptome analysis identified 18 genes in secretory pathways correlating with increased sulfatase production. Experimental validation by upregulation of a set of three key genes improved the specific enzymatic activity at varying degree up to 150-fold in another sulfatase variant, broadcasting general production benefits. We also identified a correlation between product mRNA levels and sulfatase activity that generated an increase in sulfatase activity when expressed with a weaker promoter. Furthermore, we suggest that our proposed workflow for resolving bottlenecks in cellular machineries, to be useful for improvements of cell factories for other biologics as well.
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| 8. |
- Anderhag, Per, et al.
(författare)
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Syften och tillfälligheter i högstadie- och gymnasielaborationen : en studie om hur elever handlar i relation till aktivitetens mål
- 2014
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Ingår i: NorDiNa. - : University of Oslo Library. - 1504-4556 .- 1894-1257. ; 10:1, s. 63-76
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Tidskriftsartikel (refereegranskat)abstract
- Purposes and contingencies in the lower and upper secondary school labStudies have shown that students’ awareness of the goals and purposes of the laboratory activity is important for their possibility to participate in and learn from the activity. While practical activities often have been considered to be a central part of science education, relatively few studies have examined laboratory work in situ. In this paper we addressed these issues by examining (a) what purposes are distinguished when students’ work with a laboratory assignment and (b) how these purposes are made continuous with the teacher’s aim with the assignment. The data was based on classroom observations from two ordinary laboratory settings, one from a chemistry class in lower secondary school and one from a physics class in the natural science programme in upper secondary school. Although both student groups acknowledged their teacher’s intentions with the practical and could act towards the more student centered purposes of the activity, e.g. describe what happens with the copper and measure the speed of a small vessel respectively, there were differences regarding the possibilities the students had to act toward the activity’s final aim. The results showed that these factors can be referred to the amount of purposes introduced by the teacher as well as those that arose because of contingences, and the connection of these purposes to students’ prior experiences.
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| 9. |
- Andersson, Sebastian, et al.
(författare)
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Establishing epistemic practices in students’ formulation of scientifically researchable questions in upper secondary science education
- 2019
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Ingår i: NOFA7 ABSTRACTS Stockholm University, 13 - 15 May 2019. ; , s. 24-24
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The development of students' capability to engage in scientific inquiry is part of the science curricula across the educational system. However, previous research shows that laboratory and practical work in science education do not necessarily develop the capability to engage in scientific inquiry or contribute to developing an understanding of the nature of inquiry. The purpose of this study is to explore how teaching activities can be designed with a specific focus to develop students' capability to formulate questions for scientific inquiry. Some science education research points to that in order for students to develop an understanding of the nature of science inquiry, teaching has to include activities explicitly focusing aspects of inquiry such as asking questions, observing and making inferences. In this study we draw on the theoretical framework of epistemic practices to analyse and design teaching with the purpose of developing students' capabilities to formulate questions for scientific inquiry. Epistemic practices refer to the ways people in a specific community propose, justify, evaluate and legitimize knowledge claims within a disciplinary framework. From this perspective, formulating scientifically researchable questions makes sense only as part of epistemic practice in relation to a motive of knowledge production. The research question is: How can epistemic practices be established in upper-secondary school science where students are invited to participate in activities of formulating researchable questions?The study was carried out as a design-based research collaboration with a research team consisting of nine science teachers and four science education researchers. Data was collected in three cycles of design, intervention and analysis of research lessons with six classes in three different upper-secondary schools. The data consists of video-recordings of student interaction while engaging in tasks of formulating researchable scientific questions. The data is analysed using the didactical model of organizing purposes; distinguishing between overarching purposes and the student-orientated purposes emerging in interaction. The results indicate that the development of students’ capabilities to formulate researchable questions is situated in the processes of interaction with peers, and the conditions for situating the formulation of questions in a practice characterised by closeness to an epistemic object and gathering of observational data. Based on the results, we argue for a shift in science education from focusing students’ views of a generic nature of science or nature of science inquiry to focussing student participation in epistemic practices of various kinds.
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| 10. |
- Andersson, Sebastian, et al.
(författare)
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Students’ capabilities to formulate scientifically researchable questions in upper secondary science education
- 2019
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Ingår i: NOFA7 ABSTRACTS Stockholm University, 13 - 15 May 2019. ; , s. 25-25
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- A goal for science education is to develop student capabilities to participate in scientific inquiry. This includes various aspects of inquiry; formulating scientifically researchable questions as well as planning, performing, analyzing and presenting science investigations. In science education practices, there is a tradition of using practical or laboratory work to illustrate science concepts; focussing correct answers and reproduction of ready-made scientific knowledge, rather than engaging students in inquiry. Previous research shows that inquiry teaching predominantly engage students in investigating science questions as formulated beforehand by the teacher or a textbook. Little attention has been paid to what might characterize the capability of formulating scientifically researchable questions in school. In this study we draw on a theoretical framework of epistemic practices. Epistemic practices refer to the ways people in a specific community propose, justify, evaluate and legitimize knowledge claims within a disciplinary framework. From this perspective, formulating and developing scientifically researchable questions makes sense only in relation to a motive of knowledge production. The aim of this study is to explore what might characterize students’ capabilities to formulate and develop scientifically researchable questions in upper secondary science education.The collected data consists of video-recordings of student interaction in group-work focussing formulating and developing scientifically researchable questions. Data was collected as part of a design-based study with six classes in three different schools. The video-recordings were transcribed in verbatim and analysed by the means of qualitative content analysis. The preliminary results suggest three themes: Formulation of scientifically researchable questions as:1) Working with the specification of the epistemic object. The theme illustrates how the students elaborated on the meaning of related scientific concepts and discussed cause and effect. 2) Specifying researchability by focussing on how to operationalize the epistemic object. The theme illustrates how the students reformulate their questions as part of a process of discussing e.g. measurability and variables.3) Making value-judgements of epistemic objects. The theme illustrates how the students distinguish between scientific and non-scientific questions and make value-judgements about relevance. The results contribute to an understanding of what the capability to engage in scientific inquiry as participation in collective epistemic work in an upper-secondary school science classroom might entail. The themes are related to the establishing of a specific scientific epistemic object. The results are discussed in relation to previous research in science education and the development of resources for teaching inquiry framing capabilities of inquiry as generic.
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| 11. |
- Bill-Axelson, Anna, et al.
(författare)
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Radical prostatectomy versus watchful waiting in early prostate cancer
- 2005
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 352:19, s. 1977-1944
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:In 2002, we reported the initial results of a trial comparing radical prostatectomy with watchful waiting in the management of early prostate cancer. After three more years of follow-up, we report estimated 10-year results.METHODS:From October 1989 through February 1999, 695 men with early prostate cancer (mean age, 64.7 years) were randomly assigned to radical prostatectomy (347 men) or watchful waiting (348 men). The follow-up was complete through 2003, with blinded evaluation of the causes of death. The primary end point was death due to prostate cancer; the secondary end points were death from any cause, metastasis, and local progression.RESULTS:During a median of 8.2 years of follow-up, 83 men in the surgery group and 106 men in the watchful-waiting group died (P=0.04). In 30 of the 347 men assigned to surgery (8.6 percent) and 50 of the 348 men assigned to watchful waiting (14.4 percent), death was due to prostate cancer. The difference in the cumulative incidence of death due to prostate cancer increased from 2.0 percentage points after 5 years to 5.3 percentage points after 10 years, for a relative risk of 0.56 (95 percent confidence interval, 0.36 to 0.88; P=0.01 by Gray's test). For distant metastasis, the corresponding increase was from 1.7 to 10.2 percentage points, for a relative risk in the surgery group of 0.60 (95 percent confidence interval, 0.42 to 0.86; P=0.004 by Gray's test), and for local progression, the increase was from 19.1 to 25.1 percentage points, for a relative risk of 0.33 (95 percent confidence interval, 0.25 to 0.44; P<0.001 by Gray's test).CONCLUSIONS:Radical prostatectomy reduces disease-specific mortality, overall mortality, and the risks of metastasis and local progression. The absolute reduction in the risk of death after 10 years is small, but the reductions in the risks of metastasis and local tumor progression are substantial.
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| 12. |
- Björnhammer, Sebastian, et al.
(författare)
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Att designa epistemiska praktiker i nv-undervisningen - en studie om hur gymnasieelever producerar naturvetenskapligt undersökningsbara frågor
- 2018
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- I läroplanen för gymnasiet betonas det i de naturvetenskapliga ämnena att undervisningen ska innefatta naturvetenskapliga arbetsmetoder som att formulera och söka svar på frågor. Holmström, Pendrill et al. (2018) beskriver dock hur besparingar och en minskad tid för gymnasiets laborationsundervisning resulterat i att reformer likt denna inte fått någon genomslagskraft i lärares planering av laborationsundervisning. Den naturvetenskapliga undervisningen öppnar sällan upp för elever att formulera och utforska egna frågor (Lunde, 2015). Stort fokus läggs istället på reproduktion av redan etablerad kunskap och “rätta svar” (Andrée, 2007). När väl ansatser görs för att utforma uppgifter som ger eleverna möjlighet att utveckla förmåga till systematiskt undersökande är det inte självklart att uppgifterna faktiskt möjliggör det. Utmaningen är att utforma uppgifter som inte bara fokuserar på att eleverna ska utveckla förmåga att använda vissa tekniker och redskap för systematiskt undersökande utan att involvera eleverna i arbete med utveckla naturvetenskaplig kunskap (Bergvall, Lavett Lagerström & Andrée, 2018). Eleverna behöver få delta i aktiviteter som syftar till att synliggöra vad som kännetecknar naturvetenskapliga praktiker (Lunde, 2015; Kelly & Licona, 2018). En förutsättning för att etablera naturvetenskaplig epistemisk undervisningspraktik är enligt Kelly (2008) att eleverna får vara med och producera nya frågor och ny kunskap. Studiens syfte är att undersöka hur epistemiska praktiker kan etableras i naturvetenskaplig undervisning på gymnasiet där elever ges möjlighet att utveckla förmågan att formulera naturvetenskapligt undersökningsbara frågor. Vi har genomfört en designbaserad studie i tre iterativa cykler i ett nära samarbete mellan nio NV-lärare och sex forskare i NV-didaktik. Cyklerna har genomförts på tre gymnasieskolor i stockholmsregionen, med 60-90 deltagande elever i respektive cykel. Empiri består av videoinspelningar och ljudupptagningar från elevgruppers diskussioner under lektionerna, samt elevers skriftligt formulerade frågor. Vi har genomfört en kvalitativ innehållsanayls (Graneheim & Lundman, 2003;2017) vilket har resulterat i en variation av kvaliteter av förmågan att formulera naturvetenskapligt undersökningsbara frågor. De preliminära resultaten visar att dessa kvaliteter, som exempelvis att förhålla sig till frågans undersökningsbarhet, och hur eleverna fick möjlighet att utveckla dessa spelade roll för huruvida kunskapsproduktion eller vanemässiga handlingar etablerades i undervisningen (jfr Eriksson & Lindberg, 2016; Knorr Cetina, 2001).
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| 13. |
- Björnhammer, Sebastian, et al.
(författare)
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Vad kan elever som kan formulera naturvetenskapligt undersökningsbara frågor?
- 2020
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Ingår i: Forskning om undervisning och lärande. - 2000-9674 .- 2001-6131. ; 8:1, s. 81-104
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Tidskriftsartikel (refereegranskat)abstract
- Denna studie fokuserar på innebörder av att kunna formulera undersökningsbara frågor i naturvetenskap. Studien tar utgångspunkt i naturvetenskapligt undersökande som epistemiskt arbete. Den forskningsfråga som undersöks är: Vilka kvalitativa aspekter av kunnande kommer till uttryck i gymnasieelevers arbete med att formulera naturvetenskapligt undersökningsbara frågor? Studien har genomförts som en designbaserad studie med sex interventioner på gymnasiet där eleverna i den genomförda undervisningen har fått i uppgift att, i olika sammanhang, formulera undersökningsbara frågor. Data innefattar film- och ljudinspelningar och har analyserats med hjälp av kvalitativ innehållsanalys. Resultaten synliggör tre kvalitativa aspekter av att formulera undersökningsbara frågor: Precisering av det epistemiska objektet, Operationalisering av det epistemiska objektet samt Värdering av frågeställningen i relation till det epistemiska objektet.
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| 14. |
- Dalin, Frida, 1984-, et al.
(författare)
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Clinical and immunological characteristics of Autoimmune Addison's disease : a nationwide Swedish multicenter study
- 2017
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 102:2, s. 379-389
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Studies on clinical and immunological features of Autoimmune Addison's disease (AAD) are needed to understand the disease burden and increased mortality.OBJECTIVE: To provide upgraded data on autoimmune comorbidities, replacement therapy, autoantibody profiles and cardiovascular risk factors.DESIGN, SETTING AND PARTICIPANTS: Cross sectional, population-based study. 660 AAD patients were included utilizing the Swedish Addison Registry (SAR) 2008-2014. When analyzing cardiovascular risk factors, 3,594 individuals from the population-based survey in Northern Sweden, MONICA (MONItoring of Trends and Determinants of CArdiovascular Disease), served as controls.MAIN OUTCOME MEASURE: Prevalence of autoimmune comorbidities and cardiovascular risk factors. Autoantibodies against 13 autoantigens were determined.RESULTS: Sixty percent of the SAR cohort consisted of females. Mean age at diagnosis was significantly higher for females than for males (36.8 vs. 31.1 years). The proportion of 21-hydroxylase autoantibody positive patients was 83% and 62% of patients had one or more associated autoimmune diseases, more frequently coexisting in females (p<0.0001). AAD patients had lower BMI (p<0.0001) and prevalence of hypertension (p=0.027) compared with controls. Conventional hydrocortisone tablets were used by 89% of patients; with the mean dose 28.1±8.5 mg/day. The mean hydrocortisone equivalent dose normalized to body surface was 14.8±4.4 mg/m(2)/day. Higher hydrocortisone equivalent dose was associated with higher incidence of hypertension (p=0.046).CONCLUSIONS: Careful monitoring of AAD patients is warranted to detect associated autoimmune diseases. Contemporary Swedish AAD patients do not have increased prevalence of overweight, hypertension, T2DM or hyperlipidemia. However, high glucocorticoid replacement doses may be a risk factor for hypertension.
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| 15. |
- Eriksson, Daniel, et al.
(författare)
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Cytokine Autoantibody Screening in the Swedish Addison Registry Identifies Patients With Undiagnosed APS1
- 2018
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 103:1, s. 179-186
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Tidskriftsartikel (refereegranskat)abstract
- Context: Autoimmune polyendocrine syndrome type 1 (APS1) is a monogenic disorder that features autoimmune Addison disease as a major component. Although APS1 accounts for only a small fraction of all patients with Addison disease, early identification of these individuals is vital to prevent the potentially lethal complications of APS1.Objective: To determine whether available serological and genetic markers are valuable screening tools for the identification of APS1 among patients diagnosed with Addison disease.Design: We systematically screened 677 patients with Addison disease enrolled in the Swedish Addison Registry for autoantibodies against interleukin-22 and interferon-α4. Autoantibody-positive patients were investigated for clinical manifestations of APS1, additional APS1-specific autoantibodies, and DNA sequence and copy number variations of AIRE.Results: In total, 17 patients (2.5%) displayed autoantibodies against interleukin-22 and/or interferon-α4, of which nine were known APS1 cases. Four patients previously undiagnosed with APS1 fulfilled clinical, genetic, and serological criteria. Hence, we identified four patients with undiagnosed APS1 with this screening procedure.Conclusion: We propose that patients with Addison disease should be routinely screened for cytokine autoantibodies. Clinical or serological support for APS1 should warrant DNA sequencing and copy number analysis of AIRE to enable early diagnosis and prevention of lethal complications.
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| 16. |
- Fagman, Henrik, 1975, et al.
(författare)
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Nuclear accumulation of full-length and truncated adenomatous polyposis coli protein in tumor cells depends on proliferation.
- 2003
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Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 0950-9232 .- 1476-5594. ; 22:38, s. 6013-22
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Tidskriftsartikel (refereegranskat)abstract
- The adenomatous polyposis coli (APC) tumor suppressor is a nucleocytoplasmic protein. The nuclear accumulation of APC was recently found to vary depending on cell density, suggesting that putative APC function(s) in the nucleus is controlled by the establishment of cell contacts. We report here that the density-dependent redistribution of APC between nucleus and cytoplasm prevails in 6/6 thyroid and colorectal carcinoma cell lines. Moreover, mutated APC lacking known nuclear localization sequences had the similar distribution pattern as the full-length protein. APC invariably accumulated in the nuclei of Ki-67 expressing cells, but was largely cytoplasmic when cell cycle exit was induced by serum starvation or at high cell density. APC colocalized with beta-catenin in the nucleus only in one cell line (SW480). Also, APC maintained a predominantly nuclear position in early confluent states when cytoplasmic beta-catenin was recruited to newly formed adherens-like junctions. The results indicate that nuclear targeting of APC is driven by cell cycle entry rather than altered cell-cell contact. The ability of C-terminally truncated APC to accumulate in the nucleus suggests that nuclear import signals other than NLS1(APC) and NLS2(APC) are functionally important. Residual function(s) of N-terminal APC fragments in tumor cells carrying APC mutations might be beneficial to tumor growth and survival.
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| 18. |
- Freerks, Per, et al.
(författare)
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Att utveckla gymnasieelevers förmåga att formulera, värdera och precisera naturvetenskapligt undersökningsbara frågor
- 2018
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Tidigare forskning visar att elevers deltagande i laborationer inte självklart utvecklar förmågan till systematiskt undersökande arbete. I studien som presenteras utforskas därför hur undervisning kan bidra till att utveckla elevers förmåga att formulera naturvetenskapligt undersökningsbara frågor. Lärare från tre olika gymnasieskolor och fem ämnesdidaktiska forskare har i tre cykler tillsammans designat, implementerat och analyserat lektioner där elever engagerats i att formulera naturvetenskapligt undersökningsbara frågor. Det preliminära resultatet visar att gymnasieelever kan urskilja och diskutera flera aspekter av vad som kan känneteckna en naturvetenskapligt undersökningsbar fråga. Vidare synliggörs betydelsen av att sätta formuleringen av naturvetenskapliga frågor i relation till att också planera och genomföra en undersökning.
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| 19. |
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| 20. |
- Hellgren, Johan, 1965, et al.
(författare)
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Allergic rhinitis and the common cold--high cost to society.
- 2010
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Ingår i: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 65:6, s. 776-83
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Tidskriftsartikel (refereegranskat)abstract
- The common cold and allergic rhinitis constitute a global health problem that affects social life, sleep, school and work performance and is likely to impose a substantial economic burden on society because of absence from work and reduced working capacity. This study assesses the loss of productivity as a result of both allergic rhinitis and the common cold in the Swedish working population.
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| 21. |
- Hendrikse, Natalie, et al.
(författare)
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Ancestral lysosomal enzymes with increased activity harbor therapeutic potential for treatment of Hunter syndrome
- 2021
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Ingår i: ISCIENCE. - : Elsevier BV. - 2589-0042. ; 24:3
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Tidskriftsartikel (refereegranskat)abstract
- We show the successful application of ancestral sequence reconstruction to enhance the activity of iduronate-2-sulfatase (IDS), thereby increasing its therapeutic potential for the treatment of Hunter syndrome-a lysosomal storage disease caused by impaired function of IDS. Current treatment, enzyme replacement therapy with recombinant human IDS, does not alleviate all symptoms, and an unmet medical need remains. We reconstructed putative ancestral sequences of mammalian IDS and compared them with extant IDS. Some ancestral variants displayed up to 2-fold higher activity than human IDS in in vitro assays and cleared more substrate in ex vivo experiments in patient fibroblasts. This could potentially allow for lower dosage or enhanced therapeutic effect in enzyme replacement therapy, thereby improving treatment outcomes and cost efficiency, as well as reducing treatment burden. In summary, we showed that ancestral sequence reconstruction can be applied to lysosomal enzymes that function in concert with modern enzymes and receptors in cells.
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| 22. |
- Hendrikse, Natalie
(författare)
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Engineering enzymes towards biotherapeutic applications using ancestral sequence reconstruction
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Enzymes are versatile biocatalysts that fulfill essential functions in all forms of life and, therefore, play an important role in health and disease. One specific application of enzymes in life science is their use as biopharmaceuticals, which typically benefits from high catalytic activity and stability. Increased stability and activity are both desirable properties for biopharmaceuticals as they are directly related to dosage, which in turn affects administration time, cost of production and potency of a drug. The aim of the work presented in this thesis is to enhance the therapeutic potential of enzymes by means of enzyme engineering, in particular using ancestral sequence reconstruction. In Paper I, we established the utility of this method in a model system and obtained ancestral terpene cyclases with increased activity, stability and substrate scope. In Paper II, we described the successful crystallization of the most stable ancestral terpene cyclase, which allowed for rational design of substrate specificity. Finally, we applied the method to two therapeutically relevant enzyme families associated with rare metabolic disorders. We obtained ancestral phenylalanine/tyrosine ammonia-lyases with substantially enhanced thermostability and long-term stability in Paper III and ancestral iduronate-2-sulfatases with increased activity in Paper IV. In summary, the results presented herein highlight the potential of ancestral sequence reconstruction as a method to obtain stable enzyme scaffolds for further engineering and to enhance therapeutic properties of enzymes.
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| 23. |
- Holmberg, Lars, et al.
(författare)
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A randomized trial comparing radical prostatectomy with watchful waiting in early prostate cancer
- 2002
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 347:11, s. 781-789
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Radical prostatectomy is widely used in the treatment of early prostate cancer. The possible survival benefit of this treatment, however, is unclear. We conducted a randomized trial to address this question. METHODS: From October 1989 through February 1999, 695 men with newly diagnosed prostate cancer in International Union against Cancer clinical stage T1b, T1c, or T2 were randomly assigned to watchful waiting or radical prostatectomy. We achieved complete follow-up through the year 2000 with blinded evaluation of causes of death. The primary end point was death due to prostate cancer, and the secondary end points were overall mortality, metastasis-free survival, and local progression. RESULTS: During a median of 6.2 years of follow-up, 62 men in the watchful-waiting group and 53 in the radical-prostatectomy group died (P=0.31). Death due to prostate cancer occurred in 31 of 348 of those assigned to watchful waiting (8.9 percent) and in 16 of 347 of those assigned to radical prostatectomy (4.6 percent) (relative hazard, 0.50; 95 percent confidence interval, 0.27 to 0.91; P=0.02). Death due to other causes occurred in 31 of 348 men in the watchful-waiting group (8.9 percent) and in 37 of 347 men in the radical-prostatectomy group (10.6 percent). The men assigned to surgery had a lower relative risk of distant metastases than the men assigned to watchful waiting (relative hazard, 0.63; 95 percent confidence interval, 0.41 to 0.96). CONCLUSIONS: In this randomized trial, radical prostatectomy significantly reduced disease-specific mortality, but there was no significant difference between surgery and watchful waiting in terms of overall survival.
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| 24. |
- Holmstrom, Oscar, et al.
(författare)
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Detection of breast cancer lymph node metastases in frozen sections with a point-of care low-cost microscope scanner
- 2019
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 14:3
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Tidskriftsartikel (refereegranskat)abstract
- Background Detection of lymph node metastases is essential in breast cancer diagnostics and staging, affecting treatment and prognosis. lntraoperative microscopy analysis of sentinel lymph node frozen sections is standard for detection of axillary metastases but requires access to a pathologist for sample analysis. Remote analysis of digitized samples is an alternative solution but is limited by the requirement for high-end slide scanning equipment.Objective To determine whether the image quality achievable with a low-cost, miniature digital microscope scanner is sufficient for detection of metastases in breast cancer lymph node frozen sections.Methods Lymph node frozen sections from 79 breast cancer patients were digitized using a prototype miniature microscope scanner and a high-end slide scanner. Images were independently reviewed by two pathologists and results compared between devices with conventional light microscopy analysis as ground truth.Results Detection of metastases in the images acquired with the miniature scanner yielded an overall sensitivity of 91% and specificity of 99% and showed strong agreement when compared to light microscopy (k = 0.91). Strong agreement was also observed when results were compared to results from the high-end slide scanner (k = 0.94). A majority of discrepant cases were micrometastases and sections of which no anticytokeratin staining was available.ConclusionAccuracy of detection of metastatic cells in breast cancer sentinel lymph node frozen sections by visual analysis of samples digitized using low-cost, point-of-care microscopy is comparable to analysis of digital samples scanned using a high-end, whole slide scanner. This technique could potentially provide a workflow for digital diagnostics in resource-limited settings, facilitate sample analysis at the point-of-care and reduce the need for trained experts on-site during surgical procedures.
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| 25. |
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| 26. |
- Ingri, Johan, et al.
(författare)
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Size distribution of colloidal trace metals and organic carbon during a coastal bloom in the Baltic Sea
- 2004
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Ingår i: Marine Chemistry. - : Elsevier BV. - 0304-4203 .- 1872-7581. ; 91:1-4, s. 117-130
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Tidskriftsartikel (refereegranskat)abstract
- The physico-chemical speciation of organic carbon and selected metals was measured during a coastal bloom in Ekhagen Bay, Baltic Sea, using ultrafiltration.One important objective with the study was to see if any depletion of trace metals could be measured in the directly bioavailable fraction (<1000 Da, the soluble low molecular weight fraction, LMW) during a plankton bloom. Filters with five different cut-offs were used (1 kD (1000 Da), 5 kD, 10 kD, 100 kD and 0.22 μm) in order to delineate the size distribution of colloidal organic carbon (COC) and trace metals. During the bloom in May, LMW Al, Co, Cu, Mn and Ni concentrations decreased although the colloidal and particulate concentrations were relatively high. Data show that desorption of colloidal and particulate bound trace metals to the LMW fraction was slower than the process depleting the LMW fraction. Estimates of the maximum active uptake of Cu, Ni and Mn by the phytoplankton, and the loss of non-bioactive Al from the LMW fraction, indicate that processes other than active uptake by phytoplankton must contribute to the observed depletion of trace metals in the LMW fraction. Hence, in order to estimate the bioavailable pool of trace metals for plankton during bloom conditions, these other processes must be understood and quantified. Transparent Exopolymeric Particles (TEP, reflecting sugar-rich phytoplankton exudates) increased around eight times during the plankton bloom. We hypothesize that the formation of TEP is a process that might be important for the transfer of trace metals from the LMW to the particulate fraction during the phytoplankton bloom, but the significance of TEP for this depletion in Baltic Sea surface water remains to be shown.
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| 27. |
- Jung, Christian, et al.
(författare)
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A comparison of very old patients admitted to intensive care unit after acute versus elective surgery or intervention
- 2019
-
Ingår i: Journal of critical care. - : W B SAUNDERS CO-ELSEVIER INC. - 0883-9441 .- 1557-8615. ; 52, s. 141-148
-
Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to evaluate differences in outcome between patients admitted to intensive care unit (ICU) after elective versus acute surgery in a multinational cohort of very old patients (80 years; VIP). Predictors of mortality, with special emphasis on frailty, were assessed.Methods: In total, 5063 VIPs were induded in this analysis, 922 were admitted after elective surgery or intervention, 4141 acutely, with 402 after acute surgery. Differences were calculated using Mann-Whitney-U test and Wilcoxon test. Univariate and multivariable logistic regression were used to assess associations with mortality.Results: Compared patients admitted after acute surgery, patients admitted after elective surgery suffered less often from frailty as defined as CFS (28% vs 46%; p < 0.001), evidenced lower SOFA scores (4 +/- 5 vs 7 +/- 7; p < 0.001). Presence of frailty (CFS >4) was associated with significantly increased mortality both in elective surgery patients (7% vs 12%; p = 0.01), in acute surgery (7% vs 12%; p = 0.02).Conclusions: VIPs admitted to ICU after elective surgery evidenced favorable outcome over patients after acute surgery even after correction for relevant confounders. Frailty might be used to guide clinicians in risk stratification in both patients admitted after elective and acute surgery.
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| 28. |
- Kanter-Smoler, Gunilla, et al.
(författare)
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Clinical characterization and the mutation spectrum in Swedish adenomatous polyposis families
- 2008
-
Ingår i: BMC Medicine. - : BioMed Central. - 1741-7015. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The dominantly inherited condition familial adenomatous polyposis (FAP) is caused by germline mutations in the APC gene. Finding the causative mutations has great implications for the families. Correlating the genotypes to the phenotypes could help to improve the diagnosis and follow-up of patients.Methods: Mutation screening of APCand the clinical characterization of 96 unrelated FAP patients from the Swedish Polyposis Registry was performed. In addition to generally used mutation screening methods, analyses of splicing-affecting mutations and investigations of the presence of low-frequency mutation alleles, indicating mosaics, have been performed, as well as quantitative real-time polymerase chain reaction to detect lowered expression of APC.Results: Sixty-one different APC mutations in 81 of the 96 families were identified and 27 of those are novel. We have previously shown that 6 of the 96 patients carried biallelic MUTYH mutations. The 9 mutation-negative cases all display an attenuated or atypical phenotype. Probands with a genotype (codon 1250-1464) predicting a severe phenotype had a median age at diagnosis of 21.8 (range, 11-49) years compared with 34.4 (range, 14-57) years among those with mutations outside this region (P < 0.017). Dense polyposis (> 1000) occurred in 75% of the probands with a severe phenotype compared with 30% in those with mutations outside this region. The morbidity in colorectal cancer among probands was 25% at a mean age of 37.5 years and 29% at a mean age of 46.6 years.Conclusion: Using a variety of mutation-detection techniques, we have achieved a 100% detection frequency in classical FAP. Probands with APC mutations outside codon 1250-1464, although exhibiting a less-severe phenotype, are at high risk of having a colorectal cancer at diagnosis indicating that age at diagnosis is as important as the severity of the disease for colorectal cancer morbidity. © 2008 Kanter-Smoler et al; licensee BioMed Central Ltd.
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| 29. |
- Khorram-Manesh, Amir, 1958, et al.
(författare)
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A need for prehospital triage standardizing tool in mass casualty incidents
- 2021
-
Ingår i: Health Problems of Civilization. - : Termedia Sp. z.o.o.. - 2353-6942 .- 2354-0265.
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- There is no global consensus on the use of prehospital triage systems in mass casualty incidents. This heterogeneity constitutes a particular threat in the event of a Mass Casualty Incident (MCI), which often involves rescue personnel from different organizations or nationalities.
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| 30. |
- Khorram-Manesh, Amir, 1958, et al.
(författare)
-
A translational triage research development tool: standardizing prehospital triage decision-making systems in mass casualty incidents.
- 2021
-
Ingår i: Scandinavian journal of trauma, resuscitation and emergency medicine. - : Springer Science and Business Media LLC. - 1757-7241. ; 29:1
-
Tidskriftsartikel (refereegranskat)abstract
- There is no global consensus on the use of prehospital triage system in mass casualty incidents. The purpose of this study was to evaluate the most commonly used pre-existing prehospital triage systems for the possibility of creating one universal translational triage tool.The Rapid Evidence Review consisted of (1) a systematic literature review (2) merging and content analysis of the studies focusing on similarities and differences between systems and (3) development of a universal system.There were 17 triage systems described in 31 eligible articles out of 797 identified initially. Seven of the systems met the predesignated criteria and were selected for further analysis. The criteria from the final seven systems were compiled, translated and counted for in means of 1/7's. As a product, a universal system was created of the majority criteria.This study does not create a new triage system itself but rather identifies the possibility to convert various prehospital triage systems into one by using a triage translational tool. Future research should examine the tool and its different decision-making steps either by using simulations or by experts' evaluation to ensure its feasibility in terms of speed, continuity, simplicity, sensitivity and specificity, before final evaluation at prehospital level.
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| 31. |
- Khorram-Manesh, Amir, 1958, et al.
(författare)
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Developing a translational triage research tool: part two-evaluating the tool through a Delphi study among experts
- 2022
-
Ingår i: Scandinavian journal of trauma, resuscitation and emergency medicine. - : Springer Science and Business Media LLC. - 1757-7241. ; 30:1
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: There are different prehospital triage systems, but no consensus on what constitutes the optimal choice. This heterogeneity constitutes a threat in a mass casualty incident in which triage is used during multiagency collaboration to prioritize casualties according to the injuries' severity. A previous study has confirmed the feasibility of using a Translational Triage Tool consisting of several steps which translate primary prehospital triage systems into one. This study aims to evaluate and verify the proposed algorithm using a panel of experts who in their careers have demonstrated proficiency in triage management through research, experience, education, and practice. METHOD: Several statements were obtained from earlier reports and were presented to the expert panel in two rounds of a Delphi study. RESULTS: There was a consensus in all provided statements, and for the first time, the panel of experts also proposed the manageable number of critical victims per healthcare provider appropriate for proper triage management. CONCLUSION: The feasibility of the proposed algorithm was confirmed by experts with some minor modifications. The utility of the translational triage tool needs to be evaluated using authentic patient cards used in simulation exercises before being used in actual triage scenarios.
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| 32. |
- Khorram-Manesh, Amir, 1958, et al.
(författare)
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The implication of a translational triage tool in mass casualty incidents: part three: a multinational study, using validated patient cards.
- 2023
-
Ingår i: Scandinavian journal of trauma, resuscitation and emergency medicine. - 1757-7241. ; 31:1
-
Tidskriftsartikel (refereegranskat)abstract
- Mass casualty incidents (MCI) pose significant challenges to existing resources, entailing multiagency collaboration. Triage is a critical component in the management of MCIs, but the lack of a universally accepted triage system can hinder collaboration and lead to preventable loss of life. This multinational study uses validated patient cards (cases) based on real MCIs to evaluate the feasibility and effectiveness of a novel Translational Triage Tool (TTT) in primary triage assessment of mass casualty victims.Using established triage systems versus TTT, 163 participants (1575 times) triaged five patient cases. The outcomes were statistically compared.TTT demonstrated similar sensitivity to the Sieve primary triage method and higher sensitivity than the START primary triage system. However, the TTT algorithm had a lower specificity compared to Sieve and higher over-triage rates. Nevertheless, the TTT algorithm demonstrated several advantages due to its straightforward design, such as rapid assessment, without the need for additional instrumental interventions, enabling the engagement of non-medical personnel.The TTT algorithm is a promising and feasible primary triage tool for MCIs. The high number of over-triages potentially impacts resource allocation, but the absence of under-triages eliminates preventable deaths and enables the use of other personal resources. Further research involving larger participant samples, time efficiency assessments, and real-world scenarios is needed to fully assess the TTT algorithm's practicality and effectiveness in diverse multiagency and multinational contexts.
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| 33. |
- Lantz, Mikael, et al.
(författare)
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Immigration and the incidence of Graves' thyrotoxicosis, thyrotoxic multinodular goiter and solitary toxic adenoma
- 2009
-
Ingår i: European Journal of Endocrinology. - 1479-683X. ; 160:2, s. 201-206
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Environmental and genetic factors influence thyrotoxicosis, but how population migration affects the disease panorama is not known. fit an urban area in southern Sweden, during the years 1990 until 2003, the population increased from 232 000 to 267 000. In parallel, the proportion of inhabitants born outside Sweden increased. The aim was to investigate whether the incidence of Graves' thyrotoxicosis (GD), toxic multinodular goiter (TMNG), and solitary toxic adenoma (STA) has changed in Malmo since 1990 and to Study the influence of geographic origin. Design and method: An open label prospective registration of thyrotoxicosis, gender, age, smoking habits, and ethnic background during 2003-2005 in an urban area in southern Sweden (Malmo) was undertaken. Results: The total incidence of thyrotoxicosis has changed from 43 to 41.6 cases/100 000/year from the years 1988-1990 to 2003-2005(p-value 0.72). GD increased from 22 to 29.6 (p-value 0.0051). TMNG decreased from 16 to 9.9 (p-value 0.0011) and STA from 4.8 to 2.1. (p-value 0.0054)/100 000/year. The total incidence of GD was higher in inhabitants born Outside Sweden up to the age of 69 years and age-specific incidence showed a peak in women aged 50-59 years old in both groups. The greatest difference between immigrants and Swedes up to the age of 69 years was observed in women aged 20-29 years old. Conclusion: The incidence of GD has increased and of TMNG has decreased in Malmo since 1990. Geographic origin seems to affect the incidence of GD. Whether the observed peak in age-related incidence in women 50-59 years is explained by menopausal changes has to be further investigated.
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| 34. |
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| 35. |
- Meuller, Johan, et al.
(författare)
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Identification of genomic deletions of the APC gene in familial adenomatous polyposis by two independent quantitative techniques.
- 2004
-
Ingår i: Genetic testing. - : Mary Ann Liebert Inc. - 1090-6576 .- 1557-7473. ; 8:3, s. 248-56
-
Tidskriftsartikel (refereegranskat)abstract
- Large deletions in the APC (adenomatous polyposis coli) gene, causing familial adenomatous polyposis (FAP), cannot easily be detected by conventional mutation-detection techniques. Therefore, we have developed two independent quantitative methods for the detection of large deletions, encompassing one or more exons, of APC. Multiplex ligation-dependent probe amplification (MLPA) is performed in one reaction for the initial quantification of all APC exon copy numbers. Subsequently, quantitative real-time PCR (QRT-PCR) is used to verify the results obtained in the MLPA reaction. The identification of a deletion of the whole APC gene in a patient with classical FAP is described. The mutation was detected with the two quantitative methods and further verified on chromosomal level by the use of FISH (fluorescence in situ hybridization) on metaphase spreads. Furthermore, a large deletion covering exons 11-13 of the APC gene was detected in two apparently unrelated families. This deletion was further verified and characterized with long-range PCR. The MLPA test ensures a sensitive high-throughput screening for large deletions of the APC gene and can easily be implemented in the diagnostic testing for FAP.
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| 36. |
- Nordling, Love, 1995-, et al.
(författare)
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Contrastive Learning of Equivariant Image Representations for Multimodal Deformable Registration
- 2023
-
Ingår i: 2023 IEEE 20th International Symposium on Biomedical Imaging (ISBI). - : Institute of Electrical and Electronics Engineers (IEEE). - 9781665473583 - 9781665473590
-
Konferensbidrag (refereegranskat)abstract
- We propose a method for multimodal deformable image registration which combines a powerful deep learning approach to generate CoMIRs, dense image-like representations of multimodal image pairs, with INSPIRE, a robust framework for monomodal deformable image registration. We introduce new equivariance constraints to improve the consistency of CoMIRs under deformation. We evaluate the method on three publicly available multimodal datasets, one remote sensing, one histological, and one cytological. The proposed method demonstrates general applicability and consistently outperforms state-of-the-art registration tools \elastixname and VoxelMorph. We share source code of the proposed method and complete experimental setup as open-source at: https://github.com/MIDA-group/CoMIR_INSPIRE.
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| 37. |
- Nordling, Love, 1995-, et al.
(författare)
-
Multimodal deformable image registration using contrastive learning of equivariant image representations
- 2023
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- We propose a method for multimodal deformable image registration which combines a powerful deep learning approach to generate CoMIRs, dense image-like representations of multimodal image pairs, with INSPIRE, a robust framework for monomodal deformable image registration. We introduce new equivariance constraints to improve the consistency of CoMIRs under deformation. We evaluate the method on three publicly available multimodal datasets, one remote sensing, one histological, and one cytological. The proposed method demonstrates general applicability and consistently outperforms state-of-the-art registration tools \elastixname and VoxelMorph. We share source code of the proposed method and complete experimental setup as open-source at: https://github.com/MIDA-group/CoMIR_INSPIRE.
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| 38. |
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| 39. |
- Nordling, Sofia, 1985-, et al.
(författare)
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Enhanced protection of the renal vascular endothelium improves early outcome in kidney transplantation : Preclinical investigations in pig and mouse
- 2018
-
Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- Ischemia reperfusion injury is one of the major complications responsible for delayed graft function in kidney transplantation. Applications to reduce reperfusion injury are essential due to the widespread use of kidneys from deceased organ donors where the risk for delayed graft function is especially prominent. We have recently shown that coating of inflamed or damaged endothelial cells with a unique heparin conjugate reduces thrombosis and leukocyte recruitment. In this study we evaluated the binding capacity of the heparin conjugate to cultured human endothelial cells, to kidneys from brain-dead porcine donors, and to murine kidneys during static cold storage. The heparin conjugate was able to stably bind cultured endothelial cells with high avidity, and to the renal vasculature of explanted kidneys from pigs and mice. Treatment of murine kidneys prior to transplantation reduced platelet deposition and leukocyte infiltration 24 hours post-transplantation, and significantly improved graft function. The present study thus shows the benefits of enhanced protection of the renal vasculature during cold storage, whereby increasing the antithrombotic and anti-adhesive properties of the vascular endothelium yields improved renal function early after transplantation.
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| 40. |
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| 41. |
- Nordling, Sofia, et al.
(författare)
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Vascular repair utilising immobilised heparin conjugate for protection against early activation of inflammation and coagulation
- 2015
-
Ingår i: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 113:6, s. 1312-1322
-
Tidskriftsartikel (refereegranskat)abstract
- Ischaemia-reperfusion injury (IRI) poses a major challenge in many thrombotic conditions and in whole organ transplantation. Activation of the endothelial cells and shedding of the protective vascular glycocalyx during IRI increase the risk of innate immune activation, cell infiltration and severe thrombus formation, promoting damage to the tissue. Here, we present a novel one-step strategy to protect the vas, culature by immobilisation of a unique multi-arm heparin conjugate to the endothelium. Applying a new in vitro blood endothelial cell chamber model, the heparin conjugate was found to bind not only to primary human endothelial cells but also directly to the collagen to which the cells adhered. Incubation of hypoxic endothelial cells with freshly drawn human blood in the blood chambers elicited coagulation activation reflected by thrombin anti-thrombin formation and binding of platelets and neutrophils. Immobilisation of the heparin conjugate to the hypoxic endothelial cells created a protective coating, leading to a Significant reduction of the recruitment of blood cells and coagulation activation compared to untreated hypoxic endothelial cells. This novel approach of immobilising multi-arm heparin conjugates on the endothelial cells and collagen of the basement membrane ensures to protect the endothelium against IRI in thrombotic disorders and in transplantation.
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| 42. |
- Planting-Bergloo, Sara, 1978-, et al.
(författare)
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Att utveckla elevers förmåga att formulera undersökningsbara frågor i naturvetenskap : Mangling av en didaktisk modell
- 2021
-
Ingår i: LUMAT. - : LUMA Centre Finland. - 2323-7112. ; 9:1, s. 774-803
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Tidskriftsartikel (refereegranskat)abstract
- En viktig målsättning för naturvetenskaplig undervisning är att utveckla förmågan att formulera undersökningsbara frågor. Syftet med den här studien är att undersöka hur undervisning som utformats med hjälp av metoden Question Formulation Technique (QFT) kan stödja utveckling av elevers förmåga att formulera naturvetenskapligt undersökningsbara frågor. QFT är en modell för att utveckla elevers förmåga att formulera och värdera sina egna frågor i allmänhet. I studien prövas QFT i en svensk skolkontext och inom ramen för naturvetenskaplig undervisning. Studien genomfördes som en interventionsstudie i gymnasieskolan och inom ramen för kursen Gymnasiearbete. I kursen ska eleverna genomföra en egen naturvetenskaplig undersökning. QFT användes för att utforma undervisning som del av introduktionen till kursen. Data består av videoinspelningar av elevsamtal från undervisning som har analyserats utifrån ett pragmatiskt ramverk med organiserande syften och praktisk epistemologisk analys. Resultaten visar vilka närliggande syften som etableras i elevernas samtal om undersökningsbara frågor i undervisningen: (A) att producera så många frågor som möjligt, (B) att bedöma vilka frågor som är mest relevanta, (C) att kategorisera frågor, (D) att hitta och specificera ett undersökningsobjekt och (E) att planera för att genomföra en undersökning. Slutsatsen är att QFT kan fungera som stöd för lärares planering av undervisning om naturvetenskapligt undersökningsbara frågor under förutsättning att läraren aktivt stödjer eleverna i att uppmärksamma centrala kvaliteter avseende undersökningsbarhet och genom att binda samman närliggande syften med det övergripande syftet.
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| 43. |
- Reimark, Josefin, et al.
(författare)
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Konsten att ställa frågor. En studie om att utveckla förmågan att ställa naturvetenskapliga frågor
- 2019
-
Ingår i: LFK-19. - : Stockholm Teaching & Learning Studies (STLS). ; , s. 95-96
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Undersökande arbetssätt betonas som en viktig del i naturvetenskaplig undervisning (Hofstein & Lunetta, 2004), och elever förväntas utveckla förmågan att formulera egna frågor som en del av sitt egna undersökande (Bielik & Yarden, 2016). Den praktiska naturvetenskapliga undervisningen finner också stöd i de aktuella svenska kursplanerna för gymnasieskolans naturvetenskapliga ämnen, där undervisningen bland annat “ ska innefatta naturvetenskapliga arbetsmetoder som att formulera och söka svar på frågor” (Skolverket, 2011). Enligt en studie av Lunde, Rundgren & Chang Rundgren (2015) förekom det dock inga exempel där elever fick formulera egna undersökningsfrågor utifrån en övergripande forskningsfråga eller problemsituation. Frågan blev i samtliga fall tilldelad eleverna. Vår studie syftar därför till att undersöka om elevers förmåga att ställa naturvetenskapliga frågor kan stärkas med hjälp av en given metod. Studien utgår från användandet av Question Formulation Technique, QFT, en metod utvecklad för att stödja elevers frågeformulerande (Rothstein & Santana, 2011). QFT innebär bland annat att eleverna utifrån olika påståenden formulerar en mängd frågor som sedan bearbetas av eleverna själva utifrån delstegen; att producera frågor, förbättra frågorna, rangordna frågorna samt att med hjälp av frågorna slutligen designa en undersökning. Studien tar sin utgångspunkt i forskningsfrågan; Hur kan en metod som QFT utveckla elevers förmåga att formulera naturvetenskapliga frågor?Studien genomfördes på en gymnasieskola inom ramen för kursen gymnasiearbete. Det är den första cykeln, av totalt tre cykler, i ett större forskningsprojekt med totalt tre deltagande gymnasieskolor, nio involverade lärare och en vfu-student. Arbetet med att identifiera vad eleverna som deltog i studien samtalade om utgått från en tematisk analys, en metod för att identifiera och analysera mönster eller teman som förekommer i data. Vidare har den didaktiska modellen organiserande syften använts för identifiera huruvida elevernas egna syften överensstämmer med de av läraren för undervisningen planerade syften (Johansson & Wickman, 2011). Studiens preliminära resultat visar att elevernas genomförande av uppgiften till viss del överensstämmer med de av läraren planerade syftena. Eleverna utvecklar även egna syften med undervisningen. Vidare ser vi att en metod som QFT kan fungera som en utgångspunkt för att utveckla elevers förmåga att formulera naturvetenskapligt undersökningsbara frågor men att lärare behöver ha en öppenhet för att anpassa metoden till kontexten och elevernas behov samt att metoden bör användas i en för eleverna bekant kontext.
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| 44. |
- Stenberg, Erik, 1969-, et al.
(författare)
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En ny plattform för att lösa bostadsfrågan : En antologi om samverkan kring bo- och byggnadsfrågor
- 2019
-
Rapport (populärvet., debatt m.m.)abstract
- Bakgrund: Hur hamnade vi här (sid 16-28)av Carl-Johan Engström, Kristian Skånberg och Erik StenbergByggandet utgör en stor delav de svenska samhälleligainvesteringarna. Boendet ståri sin tur för den enskilt störstaposten i de flestas hushållsbudget.Detta gör att det sammantagethandlar om mycket stora pengaroch resursflöden kopplade tillhållbarhetsfrågor. Det rör ocksåde miljöer där de flesta människortillbringar merparten av sina liv,med alla de beröringspunkter kringsocial hållbarhet som detta för medsig. Det gör förändringar mycket angelägna.Byggandet: Kolsänka och energiproducentav Victoria Kalén och Erik Stenberg (sid 55-61)Bygg- och fastighetssektorn stårför en stor del av samhälletsutsläpp av växthusgaser. År 2015var de inhemska utsläppen avväxthusgaser ca 11,1 miljonerton koldioxidekvivalenter. Detmotsvarade 18 procent av Sverigestotala utsläpp av växthusgaser.Lägger vi till utsläppen som byggochfastighetssektorn genererarutomlands så blir totalen över 20miljoner ton koldioxidekvivalenter.Boverkets miljöindikatorer visaratt bygg- och fastighetssektornsmiljöpåverkan ökat ytterligaresedan dess. Dessutom kommervia de globala varukedjorna förbyggmaterial ytterligare uppemot 10miljoner ton koldioxidekvivalenter ini den svenska byggprocessen årligen.Ur ett konsumtionsperspektiv äralltså de byggrelaterade utsläppenännu högre.Hela rapporten:En ny plattform för att lösa bostadsfrågan är en antologi skriven av sex författare i samråd med Global Utmanings programråd för Hållbara Städer. Antologin tar avstamp i bostadsfrågan ur ett historiskt perspektiv och belyser frågan utifrån den gemensamma strategin för en hållbara omställning – Agenda 2030. Plattformen hanterar en såväl ekonomisk, som social och miljömässig omställning av ”bostadsfrågan”, det vill säga boendet, byggandet och stadsutvecklingen. Antologin innehåller dels förslaget till plattform för samverkan och dels fem bidrag som konkretiserar problem och utmaningar.
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| 45. |
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| 46. |
- Turkki, Riku, et al.
(författare)
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Breast cancer outcome prediction with tumour tissue images and machine learning
- 2019
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Ingår i: Breast Cancer Research and Treatment. - : SPRINGER. - 0167-6806 .- 1573-7217. ; 177:1, s. 41-52
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: Recent advances in machine learning have enabled better understanding of large and complex visual data. Here, we aim to investigate patient outcome prediction with a machine learning method using only an image of tumour sample as an input.Methods: Utilising tissue microarray (TMA) samples obtained from the primary tumour of patients (N=1299) within a nationwide breast cancer series with long-term-follow-up, we train and validate a machine learning method for patient outcome prediction. The prediction is performed by classifying samples into low or high digital risk score (DRS) groups. The outcome classifier is trained using sample images of 868 patients and evaluated and compared with human expert classification in a test set of 431 patients.Results: In univariate survival analysis, the DRS classification resulted in a hazard ratio of 2.10 (95% CI 1.33-3.32, p=0.001) for breast cancer-specific survival. The DRS classification remained as an independent predictor of breast cancer-specific survival in a multivariate Cox model with a hazard ratio of 2.04 (95% CI 1.20-3.44, p=0.007). The accuracy (C-index) of the DRS grouping was 0.60 (95% CI 0.55-0.65), as compared to 0.58 (95% CI 0.53-0.63) for human expert predictions based on the same TMA samples.Conclusions: Our findings demonstrate the feasibility of learning prognostic signals in tumour tissue images without domain knowledge. Although further validation is needed, our study suggests that machine learning algorithms can extract prognostically relevant information from tumour histology complementing the currently used prognostic factors in breast cancer.
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| 47. |
- Vainio, Paula, et al.
(författare)
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Phospholipase PLA2G7, associated with aggressive prostate cancer, promotes prostate cancer cell migration and invasion and is inhibited by statins
- 2011
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Ingår i: Oncotarget. - : Impact Journals LLC. - 1949-2553. ; 2:12, s. 1176-1190
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer is the second leading cause of cancer mortality in men in developed countries. Due to the heterogeneous nature of the disease, design of novel personalized treatments is required to achieve efficient therapeutic responses. We have recently identified phospholipase 2 group VII (PLA2G7) as a potential drug target especially in ERG oncogene positive prostate cancers. Here, the expression profile of PLA2G7 was studied in 1137 prostate cancer and 409 adjacent non-malignant prostate tissues using immunohistochemistry to validate its biomarker potential and putative association with disease progression. In order to reveal the molecular alterations induced by PLA2G7 impairment, lipidomic and gene expression profiling was performed in response to PLA2G7 silencing in cultured prostate cancer cells. Moreover, the antineoplastic effect of statins combined with PLA2G7 impairment was studied in prostate cancer cells to evaluate the potential of repositioning of in vivo compatible drugs developed for other indications towards anti-cancer purposes. The results indicated that PLA2G7 is a cancer-selective biomarker in 50 % of prostate cancers and associates with aggressive disease. The alterations induced by PLA2G7 silencing highlighted the potential of PLA2G7 inhibition as an anti-proliferative, pro-apoptotic and anti-migratorial therapeutic approach in prostate cancer. Moreover, the anti-proliferative effect of PLA2G7 silencing was potentiated by lipid-lowering statins in prostate cancer cells. Taken together, our results support the potential of PLA2G7 as a biomarker and a drug target in prostate cancer and present a rationale for combining PLA2G7 inhibition with the use of statins in prostate cancer management.
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| 48. |
- Volk, Anna-Luisa, et al.
(författare)
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Stratification of responders towards eculizumab using a structural epitope mapping strategy
- 2016
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- The complement component 5 (C5)-binding antibody eculizumab is used to treat patients with paroxysmal nocturnal hemoglobinuria (PNH) and atypical haemolytic uremic syndrome (aHUS). As recently reported there is a need for a precise classification of eculizumab responsive patients to allow for a safe and cost-effective treatment. To allow for such stratification, knowledge of the precise binding site of the drug on its target is crucial. Using a structural epitope mapping strategy based on bacterial surface display, flow cytometric sorting and validation via haemolytic activity testing, we identified six residues essential for binding of eculizumab to C5. This epitope co-localizes with the contact area recently identified by crystallography and includes positions in C5 mutated in non-responders. The identified epitope also includes residue W917, which is unique for human C5 and explains the observed lack of cross-reactivity for eculizumab with other primates. We could demonstrate that Ornithodorus moubata complement inhibitor (OmCI), in contrast to eculizumab, maintained anti-haemolytic function for mutations in any of the six epitope residues, thus representing a possible alternative treatment for patients non-responsive to eculizumab. The method for stratification of patients described here allows for precision medicine and should be applicable to several other diseases and therapeutics.
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| 49. |
- Wennman, Ingela, et al.
(författare)
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The clinical consequences of a pre-hospital diagnosis of stroke by the emergency medical service system. A pilot study.
- 2012
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Ingår i: Scandinavian journal of trauma, resuscitation and emergency medicine. - : Springer Science and Business Media LLC. - 1757-7241. ; 20
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Tidskriftsartikel (refereegranskat)abstract
- There is still a considerable delay between the onset of symptoms and arrival at a stroke unit for most patients with acute stroke.The aim of the study was to describe the feasibility of a pre-hospital diagnosis of stroke by an emergency medical service (EMS) nurse in terms of diagnostic accuracy and delay from dialing 112 until arrival at a stroke unit.Between September 2008 and November 2009, a subset of patients with presumed acute stroke in the pre-hospital setting were admitted by EMS staff directly to a stroke unit, bypassing the emergency department. A control group, matched for a number of background variables, was created.In all, there were 53 patients in the direct admission group, and 49 patients in the control group. The median delay from calling for an ambulance until arrival at a stroke unit was 54 minutes in the direct admission group and 289 minutes in the control group (p < 0.0001).In a comparison between the direct admission group and the control group, a final diagnosis of stroke, transient ischemic attack (TIA) or the sequelae of prior stroke was found in 85% versus 90% (NS). Among stroke patients who lived at home prior to the event, the percentage of patients that were living at home after 3 months was 71% and 62% respectively (NS).In a pilot study, the concept of a pre-hospital diagnosis of stroke by an EMS nurse was associated with relatively high diagnostic accuracy in terms of stroke-related diagnoses and a short delay to arrival at a stroke unit. These data need to be confirmed in larger studies, with a concomitant evaluation of the clinical consequences and, if possible, the level of patient satisfaction as well.
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| 50. |
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