| 1. |
- Alrutz, Marie, et al.
(author)
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Projektledning
- 2013
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Book (pop. science, debate, etc.)abstract
- Projektledning är ett yrke med egen certifiering. Det pågår en spännande utveckling inom området och det blir allt viktigare att hålla sig ajour med utvecklingen.Det övergripande målet med den här handboken är att vara en ständigt aktuell heltäckande bok om projektarbete. Innehållsmässigt täcker den både frågor som har med struktur och styrning att göra och frågor om ledning av människor och mänskliga processer i grupp. Kompetens inom projekt byggs av både kunskap och erfarenhet. Vi följer kontinuerligt aktuell forskning inom dessa områden och bjuder in intressanta forskare att medverka som författare. Vi skildrar verkliga projekt och låter erfarenheterna få plats, både de bästa erfarenheterna och de utmaningar som man tagit sig igenom.Handboken är levande och det innebär att artiklar tas bort för att ge plats för nya, i takt med att den uppdateras fortlöpande.
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| 2. |
- Creignou, Maria, et al.
(author)
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Early transfusion patterns improve the Molecular International Prognostic Scoring System (IPSS-M) prediction in myelodysplastic syndromes
- 2024
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In: Journal of Internal Medicine. - : WILEY. - 0954-6820 .- 1365-2796.
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Journal article (peer-reviewed)abstract
- Background The Molecular International Prognostic Scoring System (IPSS-M) is the new gold standard for diagnostic outcome prediction in patients with myelodysplastic syndromes (MDS). This study was designed to assess the additive prognostic impact of dynamic transfusion parameters during early follow-up. Methods We retrieved complete transfusion data from 677 adult Swedish MDS patients included in the IPSS-M cohort. Time-dependent erythrocyte transfusion dependency (E-TD) was added to IPSS-M features and analyzed regarding overall survival and leukemic transformation (acute myeloid leukemia). A multistate Markov model was applied to assess the prognostic value of early changes in transfusion patterns. Results Specific clinical and genetic features were predicted for diagnostic and time-dependent transfusion patterns. Importantly, transfusion state both at diagnosis and within the first year strongly predicts outcomes in both lower (LR) and higher-risk (HR) MDSs. In multivariable analysis, 8-month landmark E-TD predicted shorter survival independently of IPSS-M (p < 0.001). A predictive model based on IPSS-M and 8-month landmark E-TD performed significantly better than a model including only IPSS-M. Similar trends were observed in an independent validation cohort (n = 218). Early transfusion patterns impacted both future transfusion requirements and outcomes in a multistate Markov model. Conclusion The transfusion requirement is a robust and available clinical parameter incorporating the effects of first-line management. In MDS, it provides dynamic risk information independently of diagnostic IPSS-M and, in particular, clinical guidance to LR MDS patients eligible for potentially curative therapeutic intervention.
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| 3. |
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| 4. |
- Elf, Marie, et al.
(author)
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Implementation of Open Educational Resources in a nursing programme : experiences and reflections
- 2015
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In: Conference proceedings.
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Conference paper (peer-reviewed)abstract
- World leading organizations like the United Nations Educational, Scientific and Cultural Organization (UNESCO) and the Commonwealth of learning (COL) stress the pedagogical benefits for learners of using Open Educational resources (OER). The use of OER is also increasing in higher education, as well as the increased use by citizens in society. The situation of the OER impact is encouraging, but also mixed. There are two main hypotheses under investigation were (A) that OER improves student performance; and (B) that openly licensed material is used differently to other online material.In this paper, we describe the implementation process of using Open Educational Resources (OER) in the nursing programme at Dalarna University, Sweden. The project is called IMPOERS (Implementation of OERs) (Elf, et.al, 2014). The IMPOERs project will implement the use of OERs in a nursing programme at Dalarna University, Sweden. The University and its nursing programme have long engaged in e-learning, and the nursing programme has recently been awarded the European Association of Distance Teaching Universities (EADTU) E-xcellence Associates Quality Label (Ubachs 2009 Williams, Kear & Roswell 2012). The quality award was based on the creation of a roadmap for the continuous development of e-learning and the implementation of OER, as OER until that time was not very frequently used, and neither the awareness of its benefits (Santesson et al., 2012). Hence, the IMPOERs was launched with the overall aim introduce and implement OER as a pedagogical framework in the nursing programme. We also wanted to evaluate both the process and outcomes.
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| 5. |
- Elf, Marie, et al.
(author)
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Implementation of open educational resources in a nursing programme : experiences and reflections
- 2015
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In: Open learning. - : Informa UK Limited. - 0268-0513 .- 1469-9958. ; 30:3, s. 252-266
-
Journal article (peer-reviewed)abstract
- The IMPOER project (implementation of open educational resources, OER) aimed to implement OER in a nursing programme at Dalarna University, Sweden. The university and its nursing programme have long engaged in e-learning, and the nursing programme has recently been awarded the European Association of Distance Teaching Universities E-xcellence Associates Quality Label. The quality award was based on the creation of a roadmap for the continuous development of e-learning and the implementation of OER. The results of the study illustrated that overall, the students and the educators were positive about using OER. They considered that this approach was a new way of learning, and they appreciated the fact that OER were free and easy to access. However, they felt overwhelmed by the amount of material that was available and they were concerned about quality. If the use of OER is to be sustainable, a change in attitudes and practices among students and teachers is likely needed regarding the use of resources on the web.
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| 6. |
- Elf, Marie, et al.
(author)
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IMPOER Implementering av öppna lärresurser i sjuksköterskeprogrammet. Högskolan Dalarna
- 2014
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In: [Host publication title missing]. ; , s. 149-149
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Conference paper (peer-reviewed)abstract
- Ett forskningsprojekt IMPOERS har startats för att följa en cohort sjuksköterskestudenter under implementering av OER. Detta är ett av de första mer systematiska projekten i Sverige om införande av OER. Några första preliminära resultat kommer att kunna presenteras vid NU2014,hösten 2014. Bakgrund Sjuksköterskeprogrammet på Högskolan Dalarna fick i januari 2013 utmärkelsen Excellent eLärande efter genomförd utvärdering av European Association of Distance Education Universities (EADTU). I samband med utmärkelsen vill man främja användning av Open Educational Resources (OER) för fördjupat lärande och för att studenterna härigenom ska kunna ta del av den främsta internationella forskningsfronten inom området och bli delaktiga i internationella nätverk. OER är lärresurser som är tillgängliga på internet och fritt kan användas,kopieras och spridas och i många fall även bearbetas. En öppen digital lärresurs har en angivelse,eller upphovsrättslicens, som visar under vilka villkor den får användas, kopieras, spridas och bearbetas. UNESCO är en av de drivande organisationerna bakom OER rörelsen för att tillhanda hålla fri och öppen utbildning för alla. På senare år har pedagogiska fördelar lyfts fram i användningen av OER och forskning har visat att OER kan vara en stark driv för individualiserat och öppet fritt lärande. Trots att användingen av OER ökar kraftigt inom högre utbildning, inte minst internationellt, så finns det få studier som har belyst både effekter av införande av OER och själva implementeringsprocessen. Projektet syftar till att beskriva hur och på vilket sätt OER kan genomföras och användas inom en sjuksköterskeutbildning. OER kommer att implementeras och effekter och genomförandeprocessen kommer att studeras. Detta kommer att genomföras genom en blandad metod med hjälp av enkäter, dagböcker och intervjuer. Specifika frågor som vi vill besvara: Hur används OER? När används OER? Vilka OER används? Hur etableras professionella nätverk för studenterna genom användning av OER? På vilket sätt influeras kvaliteten i lärandet? Metod Vi kommer att implementera OER i en kurs inom programmet och följa dess effekter och processen att införa OER. Det kommer vi att göra genom mixad metod med hjälp av enkäter,dagboksanteckningar och intervjuer (narrativs).
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| 7. |
- Elf, Marie, et al.
(author)
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Införandet av öppna lärresurser i sjuksköterskeprogrammet - erfarenheter och reflektioner : Demonstration
- 2016
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Conference paper (other academic/artistic)abstract
- Detta projekt beskriver införandet av öppna lärresurser (OER) i sjuksköterskeprogrammet vid Högskolan Dalarna. Projektet kallas IMPOER. Sjuksköterskeprogrammet har en lång historia av att använda e-lärande och har tilldelats excellence kvalitetsackreditering av den europeiska sammanslutningen for distansundervisning inom högre utbildning (EADTU). Ackrediteringen innebar att skriva fram en plan for att kontinuerligt utveckla e-lärandet. Planen innehöll bl.a. ett mal om att satsa mer på OER. I detta projekt definieras OER som undervisnings-, inlärnings- eller forskningsmaterial som antingen ar helt fritt eller har slappts med en licens som tillåter fri användning, anpassning och distribution av material s.k.creative common license.SyfteSyftet med projektet var att införa OER och studera hur studenter och lärare upplevde användningen av OER och deras uppfattningar om hur ansatsen påverkade inlärningsprocessen.IMPOER projektetTrots att användningen av e-lärande ar etablerat i sjuksköterskeprogrammet sa ar användandet av OER inte speciellt utbrett. Kursen som valdes for IMPOER projektet var en preklinisk kurs i grundläggande omvårdnad, en kurs i andra terminen av programmet, som inkluderar både teoretiska och praktiska moment. Fokus i kursen ligger på patientens grundläggande omvårdnadsbehov, och studenterna övar på omvårdnadsaktiviteter såsom att stödja patienten med personlig hygien. Den kliniska undervisningen sker på ett kunskapscentrum, där studenterna har möjlighet att praktisera omvårdnad i en simulerad miljö med autentisk utrustning och material. I kursen ingår aven lärandemål som ar relaterade till den åldrande individen i samhället. Tidigare har inlärning skett genom imitation, vilket innebar att studenterna undervisas i tekniker och sedan imiterar pedagogen. Denna traditionella undervisningsmetod ar resurskrävande och ineffektiv. Vi ville med projektet omvända klassrummet och ge studenterna en möjlighet att bredda och fördjupa sin kunskap innan seminarier och examinationer. GenomförandetProjektet genomfördes i tre steg (1) systematisk sökning och granskning av OER som skulle kunna användas i kursen; (2) utveckling av läromedel (lärandemål, examinationsuppgifter, studieguide, videoproduktion); (3) stod till studenter och lärare att använda OER.Efter en genomgång av OER på nätet konstaterades att det fanns otillräckligt med OER som passade en svensk kontext. Projektledarna (MN, MJ) utvecklade därför in ett antal scenarier och spelade in instruktionsfilmer med stod av en medieproducent anställd vid Högskolans Dalarna. Under kursens gång uppmuntrades studenterna att använda OER och de inspelade filmerna for att förbereda sig for de praktiska examinationerna på kunskapscentrat. I en av uppgifterna ingick att skriva om individens åldrandeprocess med hjälp av OER.UtvärderingProjektet utvärderades med hjälp av semi-strukturerade intervjuer och analyserades med innehållsanalys. Resultaten visar att både studenter och lärare tyckte att det hade varit en positiv erfarenhet av att använda OER men de kände sig överväldigade av den mängd material som fanns och de var bekymrade över kvaliteten. Användningen av OER stimulerade ett kritiskt förhållningssätt. Både studenterna och lärare ansåg att ansatsen var ett stimulerande och bra satt att lära sig, och de uppskattade att det fanns OER som var fritt och lätt att komma at. Om användningen av OER skall utvecklas och bli hållbar behovs en förändring i attityder och praxis bland studenter och lärare.
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| 8. |
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| 9. |
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| 10. |
- Guzzi, Nicola, et al.
(author)
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Pseudouridine-modified tRNA fragments repress aberrant protein synthesis and predict leukaemic progression in myelodysplastic syndrome
- 2022
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In: Nature Cell Biology. - : Springer Science and Business Media LLC. - 1465-7392 .- 1476-4679. ; 24:3, s. 299-306
-
Journal article (peer-reviewed)abstract
- Transfer RNA-derived fragments (tRFs) are emerging small noncoding RNAs that, although commonly altered in cancer, have poorly defined roles in tumorigenesis1. Here we show that pseudouridylation (Ψ) of a stem cell-enriched tRF subtype2, mini tRFs containing a 5′ terminal oligoguanine (mTOG), selectively inhibits aberrant protein synthesis programmes, thereby promoting engraftment and differentiation of haematopoietic stem and progenitor cells (HSPCs) in patients with myelodysplastic syndrome (MDS). Building on evidence that mTOG-Ψ targets polyadenylate-binding protein cytoplasmic 1 (PABPC1), we employed isotope exchange proteomics to reveal critical interactions between mTOG and functional RNA-recognition motif (RRM) domains of PABPC1. Mechanistically, this hinders the recruitment of translational co-activator PABPC1-interacting protein 1 (PAIP1)3 and strongly represses the translation of transcripts sharing pyrimidine-enriched sequences (PES) at the 5′ untranslated region (UTR), including 5′ terminal oligopyrimidine tracts (TOP) that encode protein machinery components and are frequently altered in cancer4. Significantly, mTOG dysregulation leads to aberrantly increased translation of 5′ PES messenger RNA (mRNA) in malignant MDS-HSPCs and is clinically associated with leukaemic transformation and reduced patient survival. These findings define a critical role for tRFs and Ψ in difficult-to-treat subsets of MDS characterized by high risk of progression to acute myeloid leukaemia (AML).
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| 11. |
- Hattinger, Monika, 1969-, et al.
(author)
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Collaboration for lifelong-learning and contract education : towards a competence development model
- 2020
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In: VILÄR. - Trollhättan : Högskolan Väst. - 9789188847867 ; , s. 26-28
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Conference paper (other academic/artistic)abstract
- Competence development and continuous lifelong learning are increasing due to skill transformations in the surrounding world which have an impact on workplaces. Upskilling, down-skilling, re-skilling, and the need of totally new skills are intensified that changes the conditions for a sustainable work practice. Old academic degrees need to be updated and for those lacking one, employees are required to build up academic credits. A constant knowledge and skills development of employees are therefore vital for the changed work conditions, meaning for both the organization and for the individual lifelong learning. In such situation, the university can play asignificant role for educating and supporting the working life with higher education in forms that are adjusted to organizational competence needs. With contract education - CE, the Swedish universities can educate staff for competence development on all educational levels, even those without an earlier academic degree. However, only organizations (including private companies and public authorities) can commission a service from a higher education institution. Individuals are not allowed to buy a course place, which is regulated through the jurisdiction of Uppdragsförordningen 2002:760. Despite the many possibilities with CE to collaborate with the surrounding society, it put pressures on the university toorganize, support and create new routines for the teaching and administrativepersonnel for the contract educational process of customer dialogue, needs inventory, course design, implementation, and follow-up on initiatives.Given such background, a collaborative development project between six universities in Sweden was conducted between November 2017 until January 2021. Overall aim was to increase the knowledge of CE by developing a collaborative model forcompetence development. The project was designed to enhance the knowledge informs of models, methods, and documentation in three development areas for CE; 1) organization and work processes, 2) customer dialogue, needs inventory and course design, and 3) incentives and collaboration skills. Both the conditions of the university’s internal abilities, restrictions, and structures (i.e., area 1) as well as the incentives and capabilities for external organizations (customers) involved in the activities (i.e., area 2), have been in focus. Area 3 concerned the teacher’s abilities to grant collaborative qualifications by teaching and engaging with external partners.In an initial case study of area 1 and 2, and we asked: What are the university conditions for organizing contract education, and how is the educational process directing and supporting the working life knowledge requirement?The second study focused on area 3 and we asked: How does the university grant collaboration skills and qualifications for teachers and leaders involved in contract education?Study one summarized eight universities responses showing that four universities have a centralized organization for running CE of which two universities have a university enterprise for CE. The other four universities are decentralized organized. It is not clear which organization is most beneficial. However, it seems that central functions are essential for a long-term external collaboration with key customers. The variation of administrative support is large, and there are also many universities lacking a full-fledge support organization for developing sustainable internal routines as well as external collaborations. When it comes to the educational process of routines for CE, most universities in the study show a very similar process, concerning the steps of curricula development, contract development, calculation, and student admission etc. However, there are various efficiency between the universities built on volume and experience of CE, which effect the time from initialization to evaluation of a CE course. The second and small document and interview study (six interviews) was targeting the teacher’s incitement, skills, and their ability to grant contract education work as accreditation in their professional academic career. This study shows that universities generally lack support for skills acquisition regarding “collaboration” skills both for professional development and further qualification. It also shows that the six included universities in the project, have diverse documentation and work practices for collaboration skills accreditation. However, this study and the project itself have pushed, the included universities to start up evaluation of their documents and routines around accreditation.A summary report for the whole project including a competence development model and methods and as well as findings from the two studies, raises the overarching need to develop the external collaboration university – working life, as well as knowledge about the university conditions for planning, developing, and running contract education as one successful competence model for lifelong learning. Contract education is therefore argued to support work-integrated and lifelong learning through collaborative forms between university and the working life.
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| 12. |
- Jansson, Monika
(author)
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Detection of donor cells in recipient tissues after stem cell transplantation using FISH and immunophenotyping
- 2007
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Licentiate thesis (other academic/artistic)abstract
- Haematopoietic stem cell transplantation (HSCT) is curative therapy for many malignant and non-malignant diseases. Effective conditioning regimen is an important component of HSCT in order to achieve a successful engraftment and to pursue a curative treatment. Conditioning regimens consist of chemotherapy with or without total body irradiation. Despite improved techniques and invention of new drugs, HSCT is still associated with transplantation related complications that negatively affect the outcome. Mechanisms behind the engraftment and the onset of the haematopoietic stem cells (HSC) proliferation and differentiation are not fully understood. Some studies have shown an evidence for trans-differentiation of HSC to non-haematopoietic tissues, but other studies claim that it is either cell fusion or transplantation of other progenitor cells. The aims of this thesis were to investigate plasticity of donor HSC and the occurrence of tissue specific cells of donor origin in recipient using the fluorescens in situ hybridization (FISH) technique and immunophenotyping. We also studied the effect of the different conditioning regimens on the engraftment, chimerism and the outcome of HSCT in mouse model. In study I, we investigated the effect of the administration sequence of busulphan (Bu) and cyclophosphamide (Cy) on the myeloablative and immunosuppressive effects, engraftment and toxicity in mouse model. Female BALB/c mice were transplanted with syngenic male donors after Bu-Cy or Cy-Bu conditioning and followed up to 90 days after HSCT. Sex mismatch enabled assessment of chimerism by detection of Y-chromosome carrying cells using FISH. Chimerism within specific cell populations, CD11c+ dendritic and CD4+CD25+ regulatory T cells, was assessed using FISH in combination with fluorescence immuno-phenotyping. In both Bu-Cy and Cy-Bu groups, comparable levels of chimerism were detected in the bone marrow with the peak at day 60 after HSCT, and this level remained stable. In spleen, both treatments produced similar levels of chimerism, but at the end of the study the chimerism level in Bu-Cy treated animals was significantly higher compared to the Cy-Bu group. The portion of CD11c+ and CD4+CD25+ of donor origin in the spleens was significantly lower in Cy-Bu treated animals compared to the Bu-Cy group until day +40. However, until day +90 dendritic and regulatory T cells of donor origin in the Cy-Bu group slightly exceeded those in Bu-Cy treated animals. Both dendritic and regulatory T cells play an important role in graft-versus-host disease and graft-versus leukemia effect in HSCT. Immunosuppressive effect and immune reconstitution expressed as spleen cellularity were similar in both groups. Toxicity profile expressed as decrease in body weight and levels of liver enzymes was advantageous for Cy-Bu regimen. In summary, the patterns of long-term reconstitution of the bone marrow and spleen in Bu-Cy and Cy-Bu treated animals were comparable, with less liver toxicity in Cy-Bu group. Thus, altering the administration order from Bu-Cy to Cy-Bu may be beneficial in clinical use and may have positive impact on the outcome of HSCT. In study II and III, we approached the plasticity of the stem cells by combining FISH with immunophenotyping. We studied the occurrence of non-haematopotietic cells of donor origin in female recipients transplanted with male donors. We found that 2-6% of pneumocytes type II (cytokeratin +/surfactant protein A+) were carrying Y-chromosome, and thus originating from the donor. In endometrial blood vessels about 10% of endometrial endothelial cells (CD34+/VEGFR2+) were of donor origin. In conclusion, bone marrow derived donor progenitor cells may trans-differentiate to other than haematopoeitic cells.
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| 13. |
- Jansson, Monika, et al.
(author)
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Lesson learned from Implementation of OER in the nursing program, Dalarna University, Sweden (IMPOERS)
- 2014
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Conference paper (peer-reviewed)abstract
- In the project IMPOERS, we have introduced Open Education Resourses (OER) in a nursing program. OER is one of the strongest driving forces for personalized learning. In the presentation we will report the preliminary results from the project. The use of OER is increasing in higher education. UNESCO stresses the pedagogical benefits of using OER (Hylén 2012, McGreal 2013, Punie & Haché UNESCO 2012). Today, the use of the web as an open sourse for knowledge acquisition is accepted in higher education providing new pedagogical possibilities and support for competence development. This impacts on students’ and teachers’roles and responsibility for learning, creation of learning content and activities and forms for interaction. Implementation of OER can reinforce an open culture of learning and students can have more opportunities to achieve ownership of their own learning and thereby take greater responsibility for their studies, which may enhance both motivation and individualized learning. In addition, OER can improve the progression on learning and also contribute to and support a lifelong learning. Furthermore, OER may stimulate networking among the students, which can be maintained after the education period. The Nursing program at Dalarna Univeristy in Sweden has been awarded with the EADTU´s E- xcellence Associates Label (Urbach 2009). The quality award involved the creation of a roadmap for continuous development of e-learning and implementation of OER (Santesson et al., 2012). Thus, the overal goal with the IMPOERS research project was to introduce and implement the use of OER as a pedagogical framework in the nursing program at Dalarna University. The project aimed to describe how and in what way OER can be implemented and used for learning. OER was implemented in a course within the nursing program and effects and the implementation process was studied with a mixed-method approach using questionnaires and interviews. The project focused on students' participation, knowledge, empowerment, responsibility over their own learning processes and attitudes of using OER.
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| 14. |
- Jansson, Nicklas, et al.
(author)
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Tillståndet för skyddsvärda träd i Sydöstra Sverige : Resultat från regional miljöövervakning av skyddsvärda träd
- 2017
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Reports (other academic/artistic)abstract
- Grova och ihåliga träd är en av de artrikaste miljöerna i naturen. De träd av denna typ som vi har i dag ärbara en spillra av vad som förr fanns i våra skogs- och jordbrukslandskap. Därför är de organismer somlever i dessa miljöer idag till hög grad hotade och en del av dem upptagna på den nationella rödlistan. Detta är anledningen till att åtta länsstyrelser gick samman och startade en övervakning av dessa träd somhär benämns ”Skyddsvärda” träd. För att kallas ett skyddsvärt träd skall stammen vara grövre än 80 centimeter i diameter eller ha håligheter samt med en stam grövre än 40 cm i diameter. I andra sammanhangkrävs det dock att trädet är 100 cm i diameter för att kallas skyddsvärt.Det vanligaste skyddsvärda trädet är ek och i hela den studerade regionen beräknas det finnas ca 580 000skyddsvärda ekar, vilket motsvarar sex träd per kvadratkilometer. Flest ekar finns i Kalmar, Östergötlandoch Blekinge. Det näst vanligaste skyddsvärda trädet är asp tack vare att den blir ihålig i relativt unga år,och att hackspettar gärna hackar ut sina bohål i den mjuka veden. I urbana miljöer är lönnen det vanligaste skyddsvärda trädet. Flest skyddsvärda bokar finns i Skåne, Blekinge och Halland medan flest grovaaskar finns i Jönköpings län.Beräkningarna visar att för grova eller ihåliga ekar är det det nästan 60% som har en betydande igenväxning men det är 20% där igenväxningen är klassad som akut och där andra träd och buskar bedömspåverka ekarna starkt negativt. Problemet är som störst i Halland, Örebro och Kalmar län. Oftast är uppväxande lövträd det största problemet. Det finns ett stort behov av att minska vegetationstätheten runtskyddsvärda träd. De flesta ädellövträden är dock fortfarande livskraftiga. Detta visar på att det oftast inteär för sent att utföra åtgärder. När det är sly och buskar som står för igenväxningen skuggas i huvudsaknedre delen av stammen medan trädet fortfarande får solljus högre upp, vilket gör att det inte hunnit bliså stora skador på träden.Resultaten visar på att det oftast finns fler yngre ekar sk. efterträdare än grova och ihåliga ekar. Detta innebär att om vi sköter om de träd vi har, kommer antalet gamla grova ekar öka i framtiden. Eken är detvanligaste hålträdet bland ädellövträden men de flesta andra ädellövträden har en högre andel träd medhål. Då sentida studier visat att många av ekens hålträdsarter till hög grad även utnyttjar andra trädslag ärdet viktigt att värna även om andra träd i landskap där man av naturvårdsskäl arbetar med ekskötsel.
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| 17. |
- Kveton, Filip, et al.
(author)
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A graphene-based glycan biosensor for electrochemical label-free detection of a tumor-associated antibody
- 2019
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In: Sensors (Switzerland). - : MDPI AG. - 1424-8220. ; 19:24
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Journal article (peer-reviewed)abstract
- The study describes development of a glycan biosensor for detection of a tumor-associated antibody. The glycan biosensor is built on an electrochemically activated/oxidized graphene screen-printed electrode (GSPE). Oxygen functionalities were subsequently applied for covalent immobilization of human serum albumin (HSA) as a natural nanoscaffold for covalent immobilization of Thomsen-nouvelle (Tn) antigen (GalNAc-O-Ser/Thr) to be fully available for affinity interaction with its analyte—a tumor-associated antibody. The step by step building process of glycan biosensor development was comprehensively characterized using a battery of techniques (scanning electron microscopy, atomic force microscopy, contact angle measurements, secondary ion mass spectrometry, surface plasmon resonance, Raman and energy-dispersive X-ray spectroscopy). Results suggest that electrochemical oxidation of graphene SPE preferentially oxidizes only the surface of graphene flakes within the graphene SPE. Optimization studies revealed the following optimal parameters: activation potential of +1.5 V vs. Ag/AgCl/3 M KCl, activation time of 60 s and concentration of HSA of 0.1 g L−1. Finally, the glycan biosensor was built up able to selectively and sensitively detect its analyte down to low aM concentration. The binding preference of the glycan biosensor was in an agreement with independent surface plasmon resonance analysis.
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| 18. |
- Lindberg, Monika, et al.
(author)
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Employer representatives’ experiences of supporting employees with cognitive impairments in a digital work environment
- 2024
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In: Work. - : IOS Press. - 1051-9815 .- 1875-9270.
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Journal article (peer-reviewed)abstract
- BACKGROUND: Digital work poses cognitive demands on all employees, but the impact is greater for employees with cognitive impairments. Digitalization also has significant implications for employer representatives as they are responsible for the work environment. However, knowledge is scarce concerning employer representatives’ perspectives on identifying needs and support for employees with cognitive impairments working in a digital work environment.OBJECTIVE: To describe employer representatives’ experiences of work environment management with focus on employees with cognitive impairments working in a digital environment.METHODS:Focus group methodology was used. Six employer representatives with work environment responsibilities participated.RESULTS: One overall theme “Mastering the interconnected processes in a transformative digital work environment” as well as three themes “Facilitating good digital work conditions”, “Identifying needs and difficulties in work tasks among employees’ with cognitive impairments” and “Pursuing knowledge and collaborations to support employees with cognitive impairments” with subthemes were identified. The themes describe employer representatives’ challenges and efforts to identify fluctuating needs in employees with cognitive impairments and, also, to organize and reduce cognitive demands in the work environment to support them.CONCLUSIONS: Managing the challenges of an evolving digital work environment and matching individual work ability of employees with cognitive impairments in relation to cognitive demands is an ongoing process. The participants valued cooperation with employees with cognitive impairments but lacked support from expertise. The need to develop and implement a functioning support system for vocational rehabilitation to ensure a sustainable work in digital work environments is indicated.
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| 19. |
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| 20. |
- Malcovati, Luca, et al.
(author)
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SF3B1 mutation identifies a distinct subset of myelodysplastic syndrome with ring sideroblasts
- 2015
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In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 126:2, s. 233-241
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Journal article (peer-reviewed)abstract
- Refractory anemia with ring sideroblasts (RARS) is a myelodysplastic syndrome (MDS) characterized by isolated erythroid dysplasia and 15% or more bone marrow ring sideroblasts. Ring sideroblasts are found also in other MDS subtypes, such as refractory cytopenia with multilineage dysplasia and ring sideroblasts (RCMD-RS). A high prevalence of somatic mutations of SF3B1 was reported in these conditions. To identify mutation patterns that affect disease phenotype and clinical outcome, we performed a comprehensive mutation analysis in 293 patients with myeloid neoplasm and 1% or more ring sideroblasts. SF3B1 mutations were detected in 129 of 159 cases (81%) of RARS or RCMD-RS. Among other patients with ring sideroblasts, lower prevalence of SF3B1 mutations and higher prevalence of mutations in other splicing factor genes were observed (P < .001). In multivariable analyses, patients with SF3B1 mutations showed significantly better overall survival (hazard ratio [HR], .37; P = .003) and lower cumulative incidence of disease progression (HR = 0.31; P = .018) compared with SF3B1-unmutated cases. The independent prognostic value of SF3B1 mutation was retained in MDS without excess blasts, as well as in sideroblastic categories (RARS and RCMD-RS). Among SF3B1-mutated patients, coexisting mutations in DNA methylation genes were associated with multilineage dysplasia (P = .015) but had no effect on clinical outcome. TP53 mutations were frequently detected in patients without SF3B1 mutation, and were associated with poor outcome. Thus, SF3B1 mutation identifies a distinct MDS subtype that is unlikely to develop detrimental subclonal mutations and is characterized by indolent clinical course and favorable outcome.
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| 21. |
- Mareschal, Sylvain, et al.
(author)
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Challenging conventional karyotyping by next-generation karyotyping in 281 intensively treated patients with AML
- 2021
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In: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 5:4, s. 1003-1016
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Journal article (peer-reviewed)abstract
- Although copy number alterations (CNAs) and translocations constitute the backbone of the diagnosis and prognostication of acute myeloid leukemia (AML), techniques used for their assessment in routine diagnostics have not been reconsidered for decades. We used a combination of 2 next-generation sequencing-based techniques to challenge the currently recommended conventional cytogenetic analysis (CCA), comparing the approaches in a series of 281 intensively treated patients with AML. Shallow whole-genome sequencing (sWGS) outperformed CCA in detecting European Leukemia Net (ELN)-defining CNAs and showed that CCA overestimated monosomies and suboptimally reported karyotype complexity. Still, the concordance between CCA and sWGS for all ELN CNA-related criteria was 94%. Moreover, using in silico dilution, we showed that 1 million reads per patient would be enough to accurately assess ELN-defining CNAs. Total genomic loss, defined as a total loss 200 Mb by sWGS, was found to be a better marker for genetic complexity and poor prognosis compared with the CCA-based definition of complex karyotype. For fusion detection, the concordance between CCA and whole-transcriptome sequencing (WTS) was 99%. WTS had better sensitivity in identifying inv(16) and KMT2A rearrangements while showing limitations in detecting lowly expressed PML-RARA fusions. Ligation-dependent reverse transcription polymerase chain reaction was used for validation and was shown to be a fast and reliable method for fusion detection. We conclude that a next-generation sequencing-based approach can replace conventional CCA for karyotyping, provided that efforts are made to cover lowly expressed fusion transcripts.
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| 22. |
- Mollgard, Lars, et al.
(author)
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Clinical effect of increasing doses of lenalidomide in high-risk myelodysplastic syndrome and acute myeloid leukemia with chromosome 5 abnormalities
- 2011
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In: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 96:7, s. 963-971
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Journal article (peer-reviewed)abstract
- Background Patients with chromosome 5 abnormalities and high-risk myelodysplastic syndromes or acute myeloid leukemia have a poor outcome. We hypothesized that increasing doses of lenalidomide may benefit this group of patients by inhibiting the tumor clone, as assessed by fluorescence in situ hybridization for del(5q31). Design and Methods Twenty-eight patients at diagnosis or with relapsed disease and not eligible for standard therapy (16 with acute myeloid leukemia, 12 with intermediate-risk 2 or high-risk myelodysplastic syndrome) were enrolled in this prospective phase II multicenter trial and treated with lenalidomide up to 30 mg daily for 16 weeks. Three patients had isolated del(5q), six had del(5q) plus one additional aberration, 14 had del(5q) and a complex karyotype, four had monosomy 5, and one had del(5q) identified by fluorescence in situ hybridization only. Results Major and minor cytogenetic responses, assessed by fluorescence in situ hybridization, were achieved in 5/26 (19%) and 2/26 (8%) patients, respectively, who received one or more dose of lenalidomide, while two patients achieved only a bone marrow response. Nine of all 26 patients (35%) and nine of the ten who completed the 16 weeks of trial responded to treatment. Using the International Working Group criteria for acute myeloid leukemia and myelodysplastic syndrome the overall response rate in treated patients with acute myeloid leukemia was 20% (3/15), while that for patients with myelodysplastic syndrome was 36% (4/11). Seven patients stopped therapy due to progressive disease and nine because of complications, most of which were disease-related. Response rates were similar in patients with isolated del(5q) and in those with additional aberrations. Interestingly, patients with TP53 mutations responded less well than those without mutations (2/13 versus 5/9, respectively; P = 0.047). No responses were observed among 11 cases with deleterious TP53 mutations. Conclusions Our data support a role for higher doses of lenalidomide in poor prognosis patients with myelodysplastic syndrome and acute myeloid leukemia with deletion 5q. (Clinicaltrials.gov identifier NCT00761449).
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| 23. |
- Stenqvist, Monika, et al.
(author)
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Cochlear changes after lateral and posterior semicircular canal destruction in healthy and previously toxin exposed rats : An electrophysiological and morphological investigation
- 1997
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In: Acta Oto-Laryngologica. - : Informa UK Limited. - 0001-6489 .- 1651-2251. ; 117:5, s. 681-688
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Journal article (peer-reviewed)abstract
- One group of Sprague-Dawley rats (group A, n = 6) was treated by instilling Pseudomonas aeruginosa exotoxin A (PaExoA), and another (group B, n = 6) treated similarly with Haemophilus influenzae type b endotoxin (HiBEndo). In group A a 20 dB hearing loss was observed, predominantly in the high-frequency region, which was reversible within 1 month. In group B no significant hearing impairment was noted. Between 1 and 6 months later, the lateral and posterior semicircular canals (SCCs) were ablated unilaterally. Control rats (group C, n = 8) were subjected to ablation only. All rats were cochleotomized contralaterally prior to labyrinthine surgery. Frequency-specific evoked potential testing at 2-31.5 kHz tone bursts was performed before and directly after surgery, 6, 24 and 48 hours and 1, 4 and 16 weeks postoperatively. After surgery in 18 rats, thresholds rose immediately, predominantly at 2, 4 and 6 kHz, followed by varying degrees of recovery. Greatest immediate postoperative hearing loss was observed in group A; no rat recovered completely and two rats showed severe permanent threshold elevation. All group B rats recovered completely, except one showing moderate threshold impairment. No permanent hearing loss was observed in group C. This study shows that destruction of SCCs in rats does not necessarily cause permanent hearing loss, even if the fluid spaces are not sealed off. However, previous exposure of the middle ear to PaExoA (but not HiBEndo) renders the cochlea more vulnerable and can result in persistent hearing loss.
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| 24. |
- Strömberg, Anna, et al.
(author)
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Bone marrow derived cells in adult skeletal muscle tissue in humans
- 2013
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In: Skeletal Muscle. - : Springer Science and Business Media LLC. - 2044-5040. ; 3:1, s. 12-
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Journal article (peer-reviewed)abstract
- BACKGROUND:During the past decade, several animal studies have demonstrated that in addition to local cells, cells from the bone marrow (BM) possess the ability to contribute to regeneration of injured skeletal muscle tissue. In addition, in mice, regular physical activity has been displayed to be a sufficient stimulus for BM-derived cell contribution to the muscle, indicating that this is part of the ongoing physiological remodeling of skeletal muscle. However, whether BM-derived cells participate in human skeletal muscle remodeling is not known. To this end, we analyzed the incorporation of BM-derived cells in healthy human skeletal muscle in women transplanted with male BM.METHODS:Skeletal muscle biopsies were obtained from the m. vastus lateralis of women transplanted with male donor hematopoietic stem cells 6 to 12 years earlier. Healthy women served as controls. Immunohistochemical staining for skeletal muscle fibers, satellite cells (SCs) or endothelial cells (ECs) combined with fluorescent in situ hybridization (FISH) of X and Y chromosomes was used to identify cells of BM origin within the biopsies. Three dimensional confocal imaging was performed to demonstrate colocalization of Y chromosome and DAPI within muscle fibers. To further investigate whether BM-derived cells incorporate into the SC niche, myoblasts were extracted from the biopsies from the transplanted women, cultured, and analyzed using XY FISH and immunocytochemistry.RESULTS:Three dimensional confocal imaging indisputably demonstrated colocalization of Y chromosome and DAPI within muscle fibers. Some Y chromosomes were found within centrally located nuclei. No Y chromosomes were detected in CD56+ SCs in the tissue sections nor in the myoblasts cultured from the extracted SCs. Y chromosome+ ECs were found in all sections from the transplanted subjects. No Y chromosomes were found in the skeletal muscle biopsies obtained from healthy control women.CONCLUSIONS:We demonstrate that BM-derived cells contribute to skeletal muscle fibers and ECs. Our results support that BM contribution to skeletal muscle occurs via direct fusion to muscle fibers, and that the contributing cells derive from the hematopoietic lineage. Thus, the present findings encourage further studies of the importance of this process for the physiological adaptation occurring throughout life.
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| 25. |
- Tibbling, Lita, et al.
(author)
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Effect of spasmolytic drugs on esophageal foreign bodies : A multicenter placebo controlled double-blind study of glucagon and diazepam
- 1995
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In: Dysphagia (New York. Print). - 0179-051X .- 1432-0460. ; 10:2, s. 126-7
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Journal article (peer-reviewed)abstract
- Muscle spasm has been proposed as the cause for esophageal food impaction. The aim was therefore to treat esophageal foreign bodies with spasmolytic drugs influencing both striated and smooth muscles of the esophagus. A multicenter, placebo-controlled, double-blind study of glucagon and diazepam was undertaken in 43 patients. The foreign body disimpacted in 9 of 24 patients given active substances and in 6 of 19 patients given placebo; there was no significant difference between these two groups. Almost all disimpactions occurred several hours after injection of the drugs. The hypothesis of muscle spasm as an important cause of esophageal obstruction was rejected. Medical therapies for food disimpaction other than spasmolytic drugs have to be investigated.
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| 26. |
- Tobiasson, Magnus, et al.
(author)
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Comprehensive mapping of the effects of azacitidine on DNA methylation, repressive/permissive histone marks and gene expression in primary cells from patients with MDS and MDS-related disease
- 2017
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In: Oncotarget. - : IMPACT JOURNALS LLC. - 1949-2553. ; 8:17, s. 28812-28825
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Journal article (peer-reviewed)abstract
- Azacitidine (Aza) is first-line treatment for patients with high-risk myelodysplastic syndromes (MDS), although its precise mechanism of action is unknown. We performed the first study to globally evaluate the epigenetic effects of Aza on MDS bone marrow progenitor cells assessing gene expression (RNA seq), DNA methylation (Illumina 450k) and the histone modifications H3K18ac and H3K9me3 (ChIP seq). Aza induced a general increase in gene expression with 924 significantly upregulated genes but this increase showed no correlation with changes in DNA methylation or H3K18ac, and only a weak association with changes in H3K9me3. Interestingly, we observed activation of transcripts containing 15 endogenous retroviruses (ERVs) confirming previous cell line studies. DNA methylation decreased moderately in 99% of all genes, with a median beta-value reduction of 0.018; the most pronounced effects seen in heterochromatin. Aza-induced hypomethylation correlated significantly with change in H3K9me3. The pattern of H3K18ac and H3K9me3 displayed large differences between patients and healthy controls without any consistent pattern induced by Aza. We conclude that the marked induction of gene expression only partly could be explained by epigenetic changes, and propose that activation of ERVs may contribute to the clinical effects of Aza in MDS.
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| 27. |
- Todisco, Gabriele, et al.
(author)
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Integrated Genomic and Transcriptomic Analysis Improves Disease Classification and Risk Stratification of MDS with Ring Sideroblasts
- 2023
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In: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 29:20, s. 4256-4267
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Journal article (peer-reviewed)abstract
- Purpose: Ring sideroblasts (RS) define the low-risk myelodysplastic neoplasm (MDS) subgroup with RS but may also reflect erythroid dysplasia in higher risk myeloid neoplasm. The benign behavior of MDS with RS (MDSRSþ) is limited to SF3B1-mutated cases without additional high-risk genetic events, but one third of MDSRSþ carry no SF3B1 mutation, suggesting that different molecular mechanisms may underlie RS formation. We integrated genomic and transcriptomic analyses to evaluate whether transcriptome profiles may improve current risk stratification. Experimental Design: We studied a prospective cohort of MDSRSþ patients irrespective of World Health Organization (WHO) class with regard to somatic mutations, copy-number alterations, and bone marrow CD34þ cell transcriptomes to assess whether transcriptome profiles add to prognostication and provide input on disease classification. Results: SF3B1, SRSF2, or TP53 multihit mutations were found in 89% of MDSRSþ cases, and each mutation category was associated with distinct clinical outcome, gene expression, and alternative splicing profiles. Unsupervised clustering analysis identified three clusters with distinct hemopoietic stem and progenitor (HSPC) composition, which only partially overlapped with mutation groups. IPSS-M and the transcriptome-defined proportion of megakaryocyte/erythroid progenitors (MEP) independently predicted survival in multivariable analysis. Conclusions: These results provide essential input on the molecular basis of SF3B1-unmutated MDSRSþ and propose HSPC quantification as a prognostic marker in myeloid neoplasms with RS.
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| 28. |
- Westberg, Lars, 1973, et al.
(author)
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Polymorphisms of the androgen receptor gene and the estrogen receptor beta gene are associated with androgen levels in women.
- 2001
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In: The Journal of clinical endocrinology and metabolism. - 0021-972X. ; 86:6, s. 2562-8
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Journal article (peer-reviewed)abstract
- To elucidate the possible role of genetic variation in androgen receptor (AR), estrogen receptor alpha (ER alpha), and ER beta on serum androgen levels in premenopausal women, the CAG repeat polymorphism of the AR gene, the TA repeat polymorphism of the ER alpha gene, and the CA repeat polymorphism of the ER beta gene were studied in a population-based cohort of 270 women. Total testosterone, free testosterone, dehydroepiandrosterone sulfate, androstenedione, 17-hydroxyprogesterone, 3 alpha-androstanediol glucuronide, 17 beta-estradiol, LH, FSH, and sex steroid hormone-binding globulin (SHBG) were measured in serum samples obtained in the follicular phase of the menstrual cycle. Women with relatively few CAG repeats in the AR gene, resulting in higher transcriptional activity of the receptor, displayed higher levels of serum androgens, but lower levels of LH, than women with longer CAG repeat sequences. The CA repeat of the ER beta gene also was associated with androgen and SHBG levels; women with relatively short repeat regions hence displayed higher hormone levels and lower SHBG levels than those with many CA repeats. In contrast, the TA repeat of the ER alpha gene was not associated with the levels of any of the hormones measured. Our results suggest that the serum levels of androgens in premenopausal women may be influenced by variants of the AR gene and the ER beta gene, respectively.
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| 29. |
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