| 1. |
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| 2. |
- Kattge, Jens, et al.
(författare)
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TRY plant trait database - enhanced coverage and open access
- 2020
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Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
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Tidskriftsartikel (refereegranskat)abstract
- Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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| 3. |
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| 4. |
- COMPAGNO STRANDBERG, MARIA, et al.
(författare)
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Evidence-based Anti-seizure Monotherapy in Newly Diagnosed Epilepsy: a New Approach
- 2020
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Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; 142:4, s. 323-332
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesTo describe the process and results of the updated Swedish practice guidelines for monotherapy in epilepsy.Materials and MethodsThe Swedish Medical Products Agency led the process together with medical experts. Evidence rating in accordance with the International League Against Epilepsy (ILAE) template was linked to the Cochrane group's GRADE system. Evidence from recently published trials and meta‐analyses was added. A national expert panel participated in the project and contributed their clinical experience.ResultsIn seizures with focal onset, carbamazepine, lamotrigine, or levetiracetam is recommended for children and adults (ILAE level A‐C for adults/Cochrane level strong for children and adults). Oxcarbazepine is an alternative for children, although its level A evidence, in a single class I trial, could relate to poor phenytoin tolerability. Eslicarbazepine acetate, lacosamide, and zonisamide are alternatives for adults and gabapentin for the elderly (ILAE level A). Carbamazepine is not a first choice for the elderly due to its high potential for interactions. In generalized epilepsy with tonic‐clonic seizures (GTC), lamotrigine, levetiracetam, and sodium valproate are recommended for children and adults (ILAE level C‐D/Cochrane level moderate‐strong) although sodium valproate is contraindicated in girls and women of childbearing age unless special considerations are met. Ethosuximide is the first choice in absence epilepsy without GTC (ILAE level A).ConclusionsLamotrigine and levetiracetam can be used as first choice for focal seizures and generalized epilepsy with GTC, suitable in all age‐groups and for both men and women. Recommendations for GTC seizures have lower evidence than those for focal seizures.
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| 5. |
- Dahlin, Anna M, 1979-, et al.
(författare)
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The role of the CpG island methylator phenotype in colorectal cancer prognosis depends on microsatellite instability screening status
- 2010
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Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 16:6, s. 1845-1855
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The aim of this study was to relate the CpG island methylator phenotype (CIMP; characterized by extensive promoter hypermethylation) to cancer-specific survival in colorectal cancer, taking into consideration relevant clinicopathologic factors, such as microsatellite instability (MSI) screening status and the BRAF V600E mutation. EXPERIMENTAL DESIGN: Archival tumor samples from 190 patients from the Northern Sweden Health and Disease Study (NSHDS) and 414 patients from the Colorectal Cancer in Umeå Study (CRUMS), including 574 with cancer-specific survival data, were analyzed for an eight-gene CIMP panel using quantitative real-time PCR (MethyLight). MSI screening status was assessed by immunohistochemistry. RESULTS: CIMP-low patients had a shorter cancer-specific survival compared with CIMP-negative patients (multivariate hazard ratio in NSHDS, 2.01; 95% confidence interval, 1.20-3.37; multivariate hazard ratio in CRUMS, 1.48; 95% confidence interval, 1.00-2.22). This result was similar in subgroups based on MSI screening status and was statistically significant in microsatellite stable (MSS) tumors in NSHDS. For CIMP-high patients, a shorter cancer-specific survival compared with CIMP-negative patients was observed in the MSS subgroup. Statistical significance was lost after adjusting for the BRAF mutation, but the main findings were generally unaffected. CONCLUSIONS: In this study, we found a poor prognosis in CIMP-low patients regardless of MSI screening status, and in CIMP-high patients with MSS. Although not consistently statistically significant, these results were consistent in two separate patient groups and emphasize the potential importance of CIMP and MSI status in colorectal cancer research.
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| 6. |
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| 7. |
- Hallböök, Tove, et al.
(författare)
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Effectiveness of the ketogenic diet used to treat resistant childhood epilepsy in Scandinavia.
- 2015
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Ingår i: European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society. - : Elsevier BV. - 1532-2130. ; 19:1, s. 29-36
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Tidskriftsartikel (refereegranskat)abstract
- This Scandinavian collaborative retrospective study of children treated with ketogenic diet (KD) highlights indications and effectiveness over two years follow-up.
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| 8. |
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| 9. |
- Wormbs, Nina, et al.
(författare)
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The challenge of abstaining in a culture of action points
- 2024
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Ingår i: npj Climate Action. - : Nature Publishing Group. - 2731-9814. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Behavioural change is necessary in order to reach a sustainable society. Sometimes this will translate into doing less and it is likely that we need to stop some things entirely. We lay out the multiple challenges of making the act of abstaining count. The issue is partly philosophical - we ask ourselves how to intellectually and semantically frame abstaining; partly practical – how can we count abstaining? It concerns a broader understanding of modernity and interrogates the ideas of progress and growth, technological change, and innovation. Abstaining will also be a moving target as expectations and demands shift over time.
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| 10. |
- Wormbs, Nina, Professor, 1968-, et al.
(författare)
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The challenge of abstaining in a culture of action points
- 2024
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Ingår i: npj Climate Action. - : Springer Nature. - 2731-9814. ; 3:1
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Behavioural change is necessary in order to reach a sustainable society. Sometimes this will translate into doing less and it is likely that we need to stop some things entirely. We lay out the multiple challenges of making the act of abstaining count. The issue is partly philosophical - we ask ourselves how to intellectually and semantically frame abstaining; partly practical – how can we count abstaining? It concerns a broader understanding of modernity and interrogates the ideas of progress and growth, technological change, and innovation. Abstaining will also be a moving target as expectations and demands shift over time.
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| 11. |
- Berge, Isak, et al.
(författare)
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A real eye-opener: Nursing home staff experiences of co-designing nursing home services together with residents
- 2022
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Ingår i: Journal of Aging Studies. - : Elsevier BV. - 0890-4065 .- 1879-193X. ; 62
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Research and healthcare services struggle to fulfil the desires and needs of nursing home residents, and there is a call for person-centredness in both research and healthcare practice. Involvement of people outside academia in research has been advocated in an effort to increase the relevance and impact of research findings for the public. However, little is known on how to involve nursing home residents in research, and the purpose of this study was, therefore, to learn from professional experiences of working with this group. More specifically, the aim of the study was to explore nursing home staff experiences of co-designing nursing home services with the residents. Method: Focus group methodology was used. A total of 17 nursing home staff members (15 women and two men) from two nursing homes participated in four focus groups. Both homogeneity and heterogeneity were strived for during recruitment. Results: The analysis is summarised in one theme and five sub-themes, describing the co-design process as an eye-opener for staff in terms of realising their own, as well as the residents', hidden abilities, and the importance of combining personal and professional knowledge of the residents in daily care and services. Conclusion: The major finding is the contribution of knowledge on how co-designing processes in nursing homes could change the dynamics of the relationships between the people involved, and that this, in turn, could realise the resources and knowledge within each person. What researchers in ageing and health can learn from the present findings is the importance of developing genuine and person-centred relationships with both nursing home residents and staff.
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| 12. |
- Berge, Isak, et al.
(författare)
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Challenging oneself on the threshold to the world of research : frail older people's experiences of involvement in research.
- 2020
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Ingår i: BMC Geriatrics. - 1471-2318 .- 1471-2318. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: User involvement of people outside academia in research is argued to increase relevance of research for society and to empower the involved lay persons. Frail older people can be a hard to reach group for research and thus an underrepresented group in research. There is a lack of knowledge how collaboration with frail older people should be best performed. Therefore, the aim of this study was to explore frail older people's experiences of involvement in research.METHODS: In this study we have invited people, 75 years of age or older screened as physically frail and who have previously participated in a study as data sources, to share their experiences by intensive interviewing. Data was collected and analysed in parallel inspired by a constructivist grounded theory approach.RESULTS: The results demonstrate how frail older people have different incentives, how their context of ageing and the unusual position of being involved in research altogether influenced how, where and in what way they wished to be involved in research. This is described in three categories: Contributing to making a difference for oneself and others, Living a frail existence and Being on somebody else's turf. The categories compose the core category, Challenging oneself on the threshold to the world of research, which symbolises the perceived distance between the frail older people themselves and the research world, but also the challenges the frail older people could go through when choosing to be involved in research.CONCLUSIONS: Frail older people have a varied capacity to participate in research, but in what way and how is difficult to know before they have been involved in the process of research. Our results advocate that it is problematic to exclude frail older people a priori and that there is a potential for new perspectives and knowledge to be shaped in the encounter and in the relationship between the researcher and the frail older person. For research to be able to cater for frail older people's needs of health services, their voices need to be heard and taken into consideration.
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| 13. |
- Berge, Isak, et al.
(författare)
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Challenging oneself on the threshold to the world of research – frail older people’s experiences of involvement in research
- 2020
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Ingår i: BMC Geriatrics. - : Springer Science and Business Media LLC. - 1471-2318. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: User involvement of people outside academia in research is argued to increase relevance of research for society and to empower the involved lay persons. Frail older people can be a hard to reach group for research and thus an underrepresented group in research. There is a lack of knowledge how collaboration with frail older people should be best performed. Therefore, the aim of this study was to explore frail older people’s experiences of involvement in research. Methods: In this study we have invited people, 75 years of age or older screened as physically frail and who have previously participated in a study as data sources, to share their experiences by intensive interviewing. Data was collected and analysed in parallel inspired by a constructivist grounded theory approach. Results: The results demonstrate how frail older people have different incentives, how their context of ageing and the unusual position of being involved in research altogether influenced how, where and in what way they wished to be involved in research. This is described in three categories: Contributing to making a difference for oneself and others, Living a frail existence and Being on somebody else’s turf. The categories compose the core category, Challenging oneself on the threshold to the world of research, which symbolises the perceived distance between the frail older people themselves and the research world, but also the challenges the frail older people could go through when choosing to be involved in research. Conclusions: Frail older people have a varied capacity to participate in research, but in what way and how is difficult to know before they have been involved in the process of research. Our results advocate that it is problematic to exclude frail older people a priori and that there is a potential for new perspectives and knowledge to be shaped in the encounter and in the relationship between the researcher and the frail older person. For research to be able to cater for frail older people’s needs of health services, their voices need to be heard and taken into consideration.
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| 14. |
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| 15. |
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| 16. |
- Berglund, Karin, et al.
(författare)
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Technology-driven discovery as a catalyst for entrepreneurial action : A case study of the implementation of information technology in a group of firms
- 2006
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Ingår i: Managing Customer Relationships on the Intenet. - : Elsevier Science ltd. Pergamon, Amsterdam, London, Oxford. - 0080441246 ; , s. 55-69
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Bokkapitel (refereegranskat)abstract
- Technological change is an important aspect of the entrepreneurial process, and this paper views both the implementation and the use of new technology as integrated parts of this process. Based on a case study of implementation of a new information technology, we identify three components in the process: discovery, planning and entrepreneurial action. The case demonstrates that planning at the beginning often is taut as the actors’ knowledge about the processes is low. However, when the process produces discoveries, the firms move from taut to loose planning, which means that establishment of plans and execution of plans tend to merge and are no longer two distinct and separate activities. The case also indicates that discoveries are an integrated part of the implementation of the new technology and that they are related to planning. The time between the event causing the discovery and the insight that the firm has found something that was largely novel can be short, a situation we label immediate discovery. But there are also situations in which there is a lead-time between the event and the insight that the firm has made a discovery, which, in turn, results in a significant lead-time between the event causing the discovery and the entrepreneurial action. This type of discovery is called postponed discovery. We can distinguish three types of entrepreneurial action that result from discoveries. These are concerned with the direction, extension, and pace of the process.
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| 17. |
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| 18. |
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| 19. |
- Berglund, Karin, et al.
(författare)
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Walking a tightrope between artistry and entrepreneurship : The stories of the Hotel Woodpecker, Otter Inn and Luna Resort
- 2007
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Ingår i: Journal of Enterprising Communities. - : Emerald. - 1750-6204 .- 1750-6212. ; 1:3, s. 268-284
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this paper is to challenge a traditional image of the content of entrepreneurship, which is associated with creativity, identity and discovery recognition.Design/methodology/approachA narrative approach is used in telling the story about the artist/entrepreneur Mikael Genberg. The story is based on interviews, newspaper material and observations. Taking this story as the point of departure, an alternative image of entrepreneurship is suggested.FindingsFirst, from a traditional Schumpeterian perspective Genberg could be portrayed as a good example of a hero entrepreneur, an archetype of the creative artist/entrepreneur. Instead Genberg in this paper is described in terms of a creative imitator. Second, the Schumpeterian “hero entrepreneur” is associated with a fixed and strong identity. This picture is challenged and replaced by a demonstration of how double or multiple identities are used in legitimizing work which is argued to be more illustrative to the content of entrepreneurship than finding the true identity of the hero entrepreneur. Third, discovery recognition from a traditional perspective is attributed to the individual, while in this case opportunity creation signifies the process of making discoveries collectively shared.Research limitations/implicationsThis study is exploratory and based on a single case, while the results cannot be taken as generalizations. Instead an alternative understanding of the content of entrepreneurship is illustrated.Originality/valueThe value of this study is the demonstration of an alternative image of the content of entrepreneurship.
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| 20. |
- Bergmark, Maria, et al.
(författare)
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Experimental nerve compression and upregulation of CPON in DRG
- 2001
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Ingår i: NeuroReport. - 1473-558X. ; 12:17, s. 3783-3786
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Tidskriftsartikel (refereegranskat)abstract
- Expression of C-terminal flanking peptide of neuropeptide Y (CPON) in DRG and cell proliferation (incorporation of BrdU) in sciatic nerve of rats following chronic nerve compression (silicone tubes with different internal diameters) was studied by immunocytochemistry. An increased number of CPON-positive neurons and cells incorporating BrdU was induced on the compressed side, most pronounced when a tight tube was used, while no cells expressed CPON or BrdU in intact nerves. The increase was transient and declined with time. Nerve compression induces transient cell proliferation in the nerve and expression of CPON in nerve cell bodies, but this is of a lesser magnitude than those following nerve transection.
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| 21. |
- Dahlin, Anna M., 1979-, et al.
(författare)
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A genome-wide association study on medulloblastoma
- 2020
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Ingår i: Journal of Neuro-Oncology. - : Springer. - 0167-594X .- 1573-7373. ; 147:2, s. 309-315
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Medulloblastoma is a malignant embryonal tumor of the cerebellum that occurs predominantly in children. To find germline genetic variants associated with medulloblastoma risk, we conducted a genome-wide association study (GWAS) including 244 medulloblastoma cases and 247 control subjects from Sweden and Denmark.Methods: Genotyping was performed using Illumina BeadChips, and untyped variants were imputed using IMPUTE2.Results: Fifty-nine variants in 11 loci were associated with increased medulloblastoma risk (p < 1 × 10–5), but none were statistically significant after adjusting for multiple testing (p < 5 × 10–8). Thirteen of these variants were genotyped, whereas 46 were imputed. Genotyped variants were further investigated in a validation study comprising 249 medulloblastoma cases and 629 control subjects. In the validation study, rs78021424 (18p11.23, PTPRM) was associated with medulloblastoma risk with OR in the same direction as in the discovery cohort (ORT = 1.59, pvalidation = 0.02). We also selected seven medulloblastoma predisposition genes for investigation using a candidate gene approach: APC, BRCA2, PALB2, PTCH1, SUFU, TP53, and GPR161. The strongest evidence for association was found for rs201458864 (PALB2, ORT = 3.76, p = 3.2 × 10–4) and rs79036813 (PTCH1, ORA = 0.42, p = 2.6 × 10–3).Conclusion: The results of this study, including a novel potential medulloblastoma risk loci at 18p11.23, are suggestive but need further validation in independent cohorts.
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| 22. |
- Dahlin, Anna M, 1979-, et al.
(författare)
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Colorectal cancer prognosis depends on T-cell infiltration and molecular characteristics of the tumor
- 2011
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Ingår i: Modern Pathology. - : Elsevier BV. - 0893-3952 .- 1530-0285. ; 24, s. 671-682
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to relate the density of tumor infiltrating T cells to cancer-specific survival in colorectal cancer, taking into consideration the CpG island methylator phenotype (CIMP) and microsatellite instability (MSI) screening status. The T-cell marker CD3 was stained by immunohistochemistry in 484 archival tumor tissue samples. T-cell density was semiquantitatively estimated and scored 1-4 in the tumor front and center (T cells in stroma), and intraepithelially (T cells infiltrating tumor cell nests). Total CD3 score was calculated as the sum of the three CD3 scores (range 3-12). MSI screening status was assessed by immunohistochemistry. CIMP status was determined by quantitative real-time PCR (MethyLight) using an eight-gene panel. We found that patients whose tumors were highly infiltrated by T cells (total CD3 score ≥7) had longer survival compared with patients with poorly infiltrated tumors (total CD3 score ≤4). This finding was statistically significant in multivariate analyses (multivariate hazard ratio, 0.57; 95% confidence interval, 0.31-1.00). Importantly, the finding was consistent in rectal cancer patients treated with preoperative radiotherapy. Although microsatellite unstable tumor patients are generally considered to have better prognosis, we found no difference in survival between microsatellite unstable and microsatellite stable (MSS) colorectal cancer patients with similar total CD3 scores. Patients with MSS tumors highly infiltrated by T cells had better prognosis compared with intermediately or poorly infiltrated microsatellite unstable tumors (log rank P=0.013). Regarding CIMP status, CIMP-low was associated with particularly poor prognosis in patients with poorly infiltrated tumors (multivariate hazard ratio for CIMP-low versus CIMP-negative, 3.07; 95% confidence interval, 1.53-6.15). However, some subset analyses suffered from low power and are in need of confirmation by independent studies. In conclusion, patients whose tumors are highly infiltrated by T cells have a beneficial prognosis, regardless of MSI, whereas the role of CIMP status in this context is less clear.
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| 23. |
- Dahlin, Anna, 1979-
(författare)
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The CpG island methylator phenotype in colorectal cancer : studies on risk and prognosis
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background Colorectal cancer (CRC) is the second most common malignancy in developed countries. The mortality is high, with nearly half of patients dying from the disease. The primary treatment of CRC is surgery, and decisions about additional treatment with chemotherapy are based mainly on tumor stage. Novel prognostic markers that identify patients at high risk of recurrence and cancer-related death are needed. The development of CRC has been described in terms of two different pathways; the microsatellite instability (MSI) and chromosomal instability (microsatellite stable, MSS) pathway. More recently, the CpG island methylator phenotype (CIMP), characterized by frequent DNA hypermethylation, has been described as an alternative pathway of tumorigenesis. The event of DNA methylation is dependent on one-carbon metabolism, in which folate and vitamin B12 have essential functions. The purpose of this thesis was to study CIMP in CRC. The specific aims were to investigate the potential role of components of one-carbon metabolism as risk factors for this subgroup of tumors, and the prognostic importance of CIMP status, taking into consideration important confounding factors, such as MSI and tumor-infiltrating T cells. Methods CRC cases and referents included in the Northern Sweden Health and Disease Study (NSHDS, 226 cases and 437 referents) and CRC cases in the Colorectal Cancer in Umeå Study (CRUMS, n=490) were studied. Prediagnostic plasma concentrations of folate and vitamin B12 were analyzed in NSHDS. In both study groups, CIMP status was determined in archival tumor tissue by real-time quantitative PCR using an eight-gene panel (CDKN2A, MLH1, CACNA1G, NEUROG1, RUNX3, SOCS1, IGF2 and CRABP1). MSI screening status and the density of tumor-infiltrating T cells were determined by immunohistochemistry. Results An inverse association was found between plasma concentrations of vitamin B12 and rectal, but not colon, cancer risk. We also found a reduced risk of CIMP-high and CIMP-low CRC in study subjects with the lowest levels of plasma folate. We found that patients with CIMP-low tumors in both NSHDS and CRUMS had a poorer prognosis compared with CIMP-negative, regardless of MSI screening status. We also found that MSS CIMP-high patients had a poorer prognosis compared with MSS CIMP-negative. The density of tumor-infiltrating T cells and CIMP status were both found to be independent predictors of CRC patient prognosis. A particularly poor prognosis was found in patients with CIMP-low tumors poorly infiltrated by T cells. In addition, the density of T cells appeared to be more important than MSI screening status for predicting CRC patient prognosis. Conclusion Rather than being one disease, CRC is a heterogeneous set of diseases with respect to clinico-pathological and molecular characteristics. We found that the association between risk and plasma concentration of vitamin B12 and folate depends on tumor site and CIMP status, respectively. Patient prognosis was found to be different depending on CIMP and MSI screening status, and the density of tumor-infiltrating T cells.
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| 24. |
- Dahlin, Christer, 1959, et al.
(författare)
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Early biocompatibility of poly (ethylene glycol) hydrogel barrier materials for guided bone regeneration. An in vitro study using human gingival fibroblasts (HGF-1).
- 2014
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Ingår i: Clinical oral implants research. - : Wiley. - 1600-0501 .- 0905-7161. ; 25:1, s. 16-20
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To evaluate the early cellular attachment and viability to modified polyethylene glycol (PEG) hydrogels with the influence of arginine-glycine-aspartic acid (RGD) in an in vitro model system. MATERIAL AND METHODS: Human gingival fibroblasts (HGF-1) were cultured on 6 different modalities of PEG hydrogel in hydrophobic polystyrene wells. A total of 7500cells/well (10000cells/cm(2) ) were dispersed over the PEG filled wells and incubated in triplicates for 24h, 7 and 13days. Cell numbers were calculated by means of a NucleoCounter. Cell viability was determined by measuring lactate dehydrogenase (LDH). For statistical analysis, nonparametric Kruska-Wallis test followed by Dunetts T3 test were used. RESULTS: All PEG modifications showed good biocompatibility, as demonstrated by low LDH values per cell at the earlier two time points. After 13days, all PEG modifications showed significantly lower number of cells compared with the controls, and the MX60 configurations demonstrated significantly higher LDH/cell values compared with the other hydrogels. CONCLUSIONS: Modifications of the physio-chemical properties of PEG hydrogels and the addition of RGD and spacers influenced the initial cellular response of cultured HGF-1 cells. With the exception of MX60 after 13days, all PEG formulations performed similarly well. Early cellular response should be considered when developing PEG-based material for clinical purposes.
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| 25. |
- Dahlin-Ivanoff, Synneve, 1950, et al.
(författare)
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Research collaboration with older people as a matter of scientific quality and ethics: a focus group study with researchers in ageing and health.
- 2024
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Ingår i: Research involvement and engagement. - : BioMed Central Ltd.. - 2056-7529. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Society is placing increasing demands on collaboration with actors outside the academia to be involved in the research process, and the responsibility for turning this into reality lies with the researchers. As research collaboration is a way to increase the societal relevance of research and since older people have the right to be actively involved in research that concerns them, this study is addressed to researchers who work with and for older people. The purpose of this article is to explore researchers' experiences of research collaboration with the heterogeneous group of older people, from healthy to frail.The focus group method was applied based on a qualitative approach that is based on a social constructivist research tradition. It differs from other qualitative methods, such as interviews, in that it encourages interaction between research participants and contributes to shedding light on a collective understanding of the world. A total of 14 researchers participated in four focus groups (three to five participants/group).The results provided support for the overall theme: "Good scientific quality and ethics are balanced against the needs and abilities of older people". This means a balance between the researcher and the older people collaborating with them to receive the best possible scientific quality. This is highlighted in the core category "Positioning for research collaboration" with the subcategories "Involvement or not", "Traditional or innovative thinking" and "Selectivity or representativeness", and the core category "Research collaboration - an ethical issue of power" with the subcategories "Research collaboration a risk for freedom of research", "Research collaboration a risk of abuse of power" and "Discriminatory academic power structures create ethical issues".Addressing the balancing act of collaborating with older people in research, the findings contribute with an understanding of the importance of researchers' awareness of social and academic structures to minimise the risk of epistemic injustices in research on ageing and health. We want to highlight the researchers' voice and clarify the role that researchers have in terms of the opportunities for older people to become part of the collective understanding of ageing and health and make their voices heard.
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| 26. |
- Dahlin-Ivanoff, Synneve, 1950, et al.
(författare)
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The multiple meaning of home as experienced by very old Swedish people.
- 2007
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Ingår i: Scandinavian journal of occupational therapy. - : Informa UK Limited. - 1103-8128 .- 1651-2014. ; 14:1, s. 25-32
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to explore aspects of the meaning of home as experienced by very old single-living people in Sweden. A grounded theory approach was used, and interviews were conducted with 40 men and women aged 80-89. The findings indicate that home has a central place in the lives of very old people because it is where they live and spend so much time. The significance of the home is based on the fact that it means so many different things to the participants. The theme comprises two key categories: home means security and home means freedom. Each of these has three sub-categories. In home means security, these are: living in a familiar neighborhood, everything functions, and having memories to live on. Home means freedom comprises a place for reflection, a social meeting-point, and leaving your own mark. Home is part of the environment and influences the meaning and selection of activities that very old people decide to engage in. When occupational therapists prescribe assistive devices or recommend changes in the home environment, they must be very well aware of and reflect on what home means to their clients and base their measures on that.
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| 27. |
- Dahlin, Joakim S., et al.
(författare)
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KIT signaling is dispensable for human mast cell progenitor development
- 2017
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 130:16, s. 1785-1794
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Tidskriftsartikel (refereegranskat)abstract
- Human hematopoietic progenitors are generally assumed to require stem cell factor (SCF) and KIT signaling during differentiation for the formation of mast cells. Imatinib treatment, which inhibits KIT signaling, depletes mast cells in vivo. Furthermore, the absence of SCF or imatinib treatment prevents progenitors from developing into mast cells in vitro. However, these observations do not mean that mast cell progenitors require SCF and KIT signaling throughout differentiation. Here, we demonstrate that circulating mast cell progenitors are present in patients undergoing imatinib treatment. In addition, we show that mast cell progenitors from peripheral blood survive, mature, and proliferate without SCF and KIT signaling in vitro. Contrary to the prevailing consensus, our results show that SCF and KIT signaling are dispensable for early mast cell development.
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| 28. |
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| 29. |
- Dahlin, Maria
(författare)
-
Nasal administration of compounds active in the central nervous system : Exploring the olfactory system
- 2000
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The nasal administration of drugs offers advantages over administration by intravenous injection. Drugs can be rapidly absorbed through the nasal mucosa, resulting in a rapid onset of action, and also avoiding degradation in the gastrointestinal tract and first-pass metabolism in the liver. The olfactory receptor cells, which are in direct contact with both the environment and the central nervous system (CNS), are potential routes for drugs into the CNS. The olfactory pathway thus circumvents the blood brain barrier (BBB) which prevents many systemically administered drugs from entering the brain.The studies used compounds active in the CNS and the experiments were performed in rodents. The nasal bioavailability of (S)-UH-301, NXX-066 and [3H]-dopamine was investigated in a rat model; uptake into the cerebrospinal fluid (CSF) was compared after nasal and intravenous administration. The concentrations of S-UH-301 and NXX-066 in plasma and CSF were measured with high performance liquid chromatography. The possible transfer of dopamine and neurotensin along the olfactory pathway after nasal administration to mice was studied using brain tissue sampling and autoradiography. The radioactivity content in blood, CSF and dissected brain tissue samples after administration of [3H]-dopamine and [3H]-neurotensin was assessed using liquid scintillation, and thin layer chromatography (TLC) was used to investigate the metabolic fate of [3H]-dopamine.The results of this thesis suggest that nasal administration of CNS-active compounds with low oral bioavailability is an interesting and workable alternative to intravenous injection. The small lipophilic compounds (S)-UH-301 and NXX-066 were rapidly and completely absorbed after nasal administration, although hard evidence of direct transfer from the nose remains elusive. Radioactivity measurements in the olfactory bulb following nasal administration of[3H]-dopamine and [3H]-neurotensin indicate that transfer occurred. The TLC results showed the presence of unchanged dopamine in the olfactory bulb but it is less clear from initial results with neurotensin, which radioactive products of this molecule reached the olfactory bulb, and further studies are required.
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| 30. |
- Dahlin, Maria
(författare)
-
Pharmacodynamics of low-dose clonazepam in children with epilepsy or spasticity : neurophysiological and clinical studies
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In children with epilepsy the evaluation of the efficacy of an antiepileptic drug (AED) is usually made by recording the seizure frequency. Some seizures are subtle and difficult to detect and epileptiform activity even without clinical seizures may cause cognitive dysfunctions. Therefore, the addition of objective quantitative methods to measure the amount of epileptiform discharges is important in the evaluation of AED effects. In clinical practice, we noticed an effect on seizure frequency and spasticity even at very low doses of the AED clonazepam (CZP). At the higher recommended doses, side effects are often prominent. The aim of these studies was to improve quantitative objective methods for measuring the pharmacodynamic effects in children with epilepsy and spasticity and, using these methods, evaluate the short-term effects of low-dose CZP, 0.02 mg/kg BW, as a single injection. In a double-blind, randomized, cross-over study of 12 children with cerebral palsy, the spastic restraint in response to low-dose CZP was quantified by means of a dynamic dynamometer and the averaged EMG activity in stretched muscles. A significant reduction of spastic restraint was demonstrated (p<0.001) at mean plasma levels of 21 nmol/L (range 11-33) during examinations. Epileptiform discharges fluctuate over time and knowing whether systematic spontaneous fluctuations occur is important for the evaluation of therapy. The number of epileptiform discharges in 24-h EEG recordings on two consecutive days and on days with an interval of a month were compared in children with epilepsy. Intraindividual changes on different days counterbalanced one another and no systematic differences were found. The variability was larger though when the interval was one month than it was on consecutive days (SD 86% and 33%). The mean magnitude of change was 55% between days separated by a month compared to 24% on consecutive days. In a double-blind, randomized, cross-over study in children with epilepsy the amount of epileptiform activity was compared on 24-h digital EEG recordings in response to low-dose CZP. A significant reduction (p=0.001 5) was found with median plasma levels ranging from 18 down to <14m- nol/L. Magnetoencephalography (MEG) was used in a pilot study of children with partial epilepsy. In 4 out of 5 children, a decrease in the magnitude of the current source generating epileptiform discharges was paralleled by a decrease in the number of discharges as well as their repetitiveness within episodes in response to low-dose CZP. In one child the opposite findings were noted. In an open study of 19 children with a high seizure frequency, a reduction of seizures was found in response to low-dose CZP (p=0.003 1) and was obtained at median maximal plasma levels of 23 nmol/L (range 11-41). In conclusion, using three objective quantitative methods, short-term effects of CZP in epilepsy and spasticity were demonstrated at doses and plasma levels well below those recommended. These dose levels could be used in the clinic for short-term treatment. The duration of effects during longterm treatment has to be determined in further studies. In studies of AEDs, it should be possible to use as a baseline day either a day immediately before or a month apart from the day of the AED examination. When evaluating AED effects in an individual child with prolonged EEGs, the large spontaneous variability must be taken into account. Our results also indicate that prolonged EEG recordings can be employed in children and that they give information concerning the extent to which an AED may influence epileptiform discharges. MEG may provide additional information. To make an optimal treatment choice taking into account both seizures and epileptiform activity, a knowledge of how different AEDs affect epileptiform discharges is needed. To measure these effects, quantitative methods of evaluation are necessary. The methodology for quantification used in these studies can be applied to other AEDs.
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| 31. |
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| 32. |
- Dahlin, Maria
(författare)
-
Tal om terror : säkerhetspolitisk retorik i Sverige och Ryssland hösten 2001
- 2008
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Aiming to facilitate the description and evaluation of rhetorical responses to security issues, a framework was developed for comparative analysis of oral and written presentations. The framework was applied on three speeches held by the Swedish Prime Minister Göran Persson and three speeches by the President of the Russian Federation Vladimir Putin in the wake of the terrorist attacks on World Trade Center and Pentagon on September 11 and the subsequent military operation in Afghanistan.The framework was based on four narrative structures, referred to as images. The image of aggression was used to describe the speaker’s interpretation of a dramatic event, the image of threat to describe his consideration of the security threat and the image of securitisation to analyse solutions suggested in relation to the threat. The image of communication, finally, was used to describe relations between the speaker and his audience appearing in the speeches. Each image included an actor, an act or event, a referent object to the act and time and space. The images were analysed as discrete parts and also by an integrating approach. In the analysis, descriptions of the images were related to rhetorical tools, including logos, pathos, ethos, identification, vividness and agency.The analyses revealed similarities and dissimilarities between the two speakers. As for similarities, Persson and Putin used similar topoi. Persson used democracy – terrorism whereas Putin preferred civilisation – terrorism/barbarism, and both used cooperation. To both speakers, the images of aggression and threat tended to appeal to pathos and identification, and the image of securitisation and communication to logos and ethos. As for dissimilarities, Persson relied on the UN whereas Putin offered direct help to the US operation. In Persson’s speeches, the predominant topos was cooperation, in Putin’s civilisation – terrorism/barbarism. Persson focused on democratic values, Putin on the fight against terrorism. Persson’s images were more elaborated and vivid, Putin’s more moderate. These dissimilarities were tentatively explained by the two speakers’ different individual styles and domestic situations and, most important, by the speakers’ different agency on the international arena.In essence, the present framework, based on four discrete images, was found to be well-suited for cross-cultural analysis of rhetorical responses to security issues. The similarities exceeded the dissimilarities, which led to the conclusion that rhetoric of security politics may be defined as a discrete rhetorical genre. A bi-polar world view pervaded the rhetoric, preventing long-term solutions to security issues. Instead a focus on cooperation topoi, nuanced information, and the means and ends of securitisation was suggested.
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| 33. |
- Dahlin, Maria, et al.
(författare)
-
Transfer of dopamine in the olfactory pathway following nasal administration in mice
- 2000
-
Ingår i: Pharmaceutical research. - 0724-8741 .- 1573-904X. ; 17:6, s. 737-742
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The aim of the study was to investigate whether dopamine is transferred along the olfactory pathway to the brain following nasal administration to mice. METHODS: [3H]-Dopamine was administered nasally or intravenously to female mice. Brain tissue samples were excised and the radioactive content was measured. The precise localisation of dopamine radioactivity in the brain was studied using autoradiography. The presence of dopamine or its metabolites in the olfactory bulb and mucosa was ascertained using thin layer chromatography (TLC). RESULTS: After administration of [3H]-dopamine into the right nostril, the amount of dopamine in the right bulb increased with time until. after 4 h, it was 27 times higher than in the left bulb. Among the other brain tissue samples, significantly higher amount of radioactivity was detected in the lateral olfactory tract. Radioactivity in the right olfactory bulb was shown by autoradiography to be selectively located in the peripheral layers 1 to 4 h after administration. Selective uptake of radioactivity was not seen in other regions of the brain. TLC data indicated that approximately 75% and 10% of the radioactivity in the olfactory bulb and mucosa, respectively, coeluted with dopamine. CONCLUSIONS: The results indicate that unchanged dopamine is transferred into the olfactory bulb following nasal administration of [3H]-dopamine.
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| 34. |
- Dahlin, Maria, 1972-
(författare)
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Tro, hopp och IT : Stora och små berättelser från ett förändringsprojekt
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Information technology (IT) is often assumed to be a prerequisite for the modern and developed organization, even though IT projects are described as problematic in practice. Starting with this paradox and using a narrative method, this study focuses on how, through their stories, employees of an organization ascribe different meanings to IT.The study, which entailed following an IT project at an insurance company, illustrates how the employees of the organization actively ascribe various and contradictory meanings to IT. On the one hand, preference is given to one grand narrative of IT as a tool in the service of the organization. This grand narrative ascribes the meaning of achieving management, control, and change, which is supposed to help the organization on its way toward a more successful future. Great responsibility is transferred to the technology for attaining the desired impact in the organization, which can backfire, especially against project management as they are hit with demands to fulfill the expectations for IT. On the other hand, employees wrestle to control the project, which they describe as unwieldy and unmanageable. The desired management, control, and change are described as elusive.The IT project has in this way come to be developed in a field of tension between contradictory meanings, where problems and solutions are constructed over time. The employees thus become, to an extent, victims of the meanings they have reproduced, something that can be described as double-edged power. The employees who were the keenest advocates of IT are also those who have the greatest difficulty accepting the failure of the technology to live up to expectations. In parallel, the study illustrates the employees’ opportunities to actively engage themselves in storytelling that complement and challenge the dominating meanings in the organization.
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| 35. |
- Dahlin, Sigrun, et al.
(författare)
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Cutting regime affects the amount and allocation of symbiotically fixed N in green manure leys
- 2010
-
Ingår i: Plant and Soil. - : Springer Science and Business Media LLC. - 0032-079X .- 1573-5036. ; 331, s. 401-412
-
Tidskriftsartikel (refereegranskat)abstract
- Cutting strategy effect on N(2) fixation and distribution of fixed N above and below ground in red clover (Trifolium pratense L.) and mixed red clover/perennial ryegrass (Lolium perenne L.) green manure leys was quantified in field experiments including in situ mezotrons and microplots. Symbiotically fixed N in clover, transfer of fixed N to grass in the mixed stands and the fate of (15)N contained in mulch were estimated by isotope dilution. Below ground clover-derived N was estimated by leaf labelling. Total N(2) fixation was estimated by correcting fixed N in plant shoots with plant-derived N below ground and recycled N from mulch. The total N(2) fixation was larger in harvested and mulched stands (average 45 g m(-2)) than in the intact stands (32 g m(-2)). Of the fixed N, 53% (intact), 46% (harvested) and 60% (mulched) was found below ground. The average recycling of N in mulch was 21% and contributed 13.7% (pure clover) and 2.2% (mixed) of the clover N in the regrowth. Recycling of N did not decrease N(2) fixation in the mulched compared with harvested stands. The results indicate that cutting regime should be considered when estimating total amounts of N fixed by green manure leys.
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| 36. |
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| 37. |
- Dahlin, Sigrun, et al.
(författare)
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Effect of wood ash and crushed rock soil amendments on red clover growth and dinitrogen fixation
- 2017
-
Ingår i: Agricultural and Food Science. - 1459-6067 .- 1795-1895. ; 26, s. 188-197
-
Tidskriftsartikel (refereegranskat)abstract
- The fertiliser effect of adding wood ash or crushed rock to a low-fertility soil, compared with an unamended control, was assessed in a pot experiment with a perennial ryegrass-red clover mixture. Dinitrogen (N-2) fixation by the clover and translocation of fixed N to the grass were determined using N-15 natural abundance. The wood ash produced the highest accumulated clover biomass over two cuts, followed by the crushed rock. Chemical analyses suggested that the increase was due to K supply by the amendments. The wood ash also led to larger amounts of fixed N compared with the control. However, N-2 fixation was not increased as much as biomass amount, leading to dilution of plant N. There were minor or no treatment effects on mineralisation from soil N pools. This indicates that good-quality wood ash can be successfully used as a multi-element soil amendment to enhance clover growth on low-fertility soils.
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| 38. |
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| 39. |
- Dahlin, Sigrun, et al.
(författare)
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Mulch N recycling in green manure leys under Scandinavian conditions
- 2011
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Ingår i: Nutrient cycling in agroecosystems. - : Springer Science and Business Media LLC. - 1385-1314 .- 1573-0867. ; 91, s. 119-129
-
Tidskriftsartikel (refereegranskat)abstract
- Nitrogen (N) recycling to the regrowth of mulched red clover (Trifolium pratense L.) and mulched mixed red clover/perennial ryegrass (Lolium perenne L.) leys was determined in field experiments during three consecutive years using (15)N-labelled shoot material. Nitrogen recycling was greater in the pure clover stands than in the mixed stands in the beginning of the growing season, but increased successively in the mixed stands so that it was similar (14-15.5%) in both stands at the end of the season. This recycling of N from the mulch led to increased biomass accumulation but did not alter stand composition in the mixed stands. Mulch-derived N was incorporated into the soil organic N in both pure clover and mixed stands which thus contributed to building up soil fertility. An approximately similar proportion of N remained unaccounted for in mulched pure clover and mixed stand leys and presumably represented gaseous losses. To exploit the benefits of green manure leys in the humid temperate zone while minimising the negative environmental impact, these should be harvested rather than mulched.
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| 40. |
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| 41. |
- Edin, Sofia, et al.
(författare)
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The Distribution of Macrophages with a M1 or M2 Phenotype in Relation to Prognosis and the Molecular Characteristics of Colorectal Cancer
- 2012
-
Ingår i: PLOS ONE. - : PLoS One. - 1932-6203. ; 7:10, s. e47045-
-
Tidskriftsartikel (refereegranskat)abstract
- High macrophage infiltration has been correlated to improved survival in colorectal cancer (CRC). Tumor associated macrophages (TAMs) play complex roles in tumorigenesis since they are believed to hold both tumor preventing (M1 macrophages) and tumor promoting (M2 macrophages) activities. Here we have applied an immunohistochemical approach to determine the degree of infiltrating macrophages with a M1 or M2 phenotype in clinical specimens of CRC in relation to prognosis, both in CRC in general but also in subgroups of CRC defined by microsatellite instability (MSI) screening status and the CpG island methylator phenotype (CIMP). A total of 485 consecutive CRC specimens were stained for nitric oxide synthase 2 (NOS2) (also denoted iNOS) as a marker for the M1 macrophage phenotype and the scavenger receptor CD163 as a marker for the M2 macrophage phenotype. The average infiltration of NOS2 and CD163 expressing macrophages along the invasive tumor front was semi-quantitatively evaluated using a four-graded scale. Two subtypes of macrophages, displaying M1 (NOS2(+)) or M2 (CD163(+)) phenotypes, were recognized. We observed a significant correlation between the amount of NOS2(+) and CD163(+) cells (P<0.0001). A strong inverse correlation to tumor stage was found for both NOS2 (P<0.0001) and CD163 (P<0.0001) infiltration. Furthermore, patients harbouring tumors highly infiltrated by NOS2+ cells had a significantly better prognosis than those infiltrated by few NOS2+ cells, and this was found to be independent of MSI screening status and CIMP status. No significant difference was found on cancer-specific survival in groups of CRC with different NOS2/CD163 ratios. In conclusion, an increased infiltration of macrophages with a M1 phenotype at the tumor front is accompanied by a concomitant increase in macrophages with a M2 phenotype, and in a stage dependent manner correlated to a better prognosis in patients with CRC.
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| 42. |
- Ekblom Bak, Elin, 1981-, et al.
(författare)
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Accelerometer derived physical activity patterns in 27.890 middle‐aged adults : The SCAPIS cohort study
- 2022
-
Ingår i: Scandinavian Journal of Medicine and Science in Sports. - : John Wiley & Sons. - 0905-7188 .- 1600-0838. ; 32:5, s. 866-880
-
Tidskriftsartikel (refereegranskat)abstract
- The present study aims to describe accelerometer-assessed physical activity (PA) patterns and fulfillment of PA recommendations in a large sample of middle-aged men and women, and to study differences between subgroups of socio-demographic, socio-economic, and lifestyle-related variables. A total of 27 890 (92.5% of total participants, 52% women, aged 50–64 years) middle-aged men and women with at least four days of valid hip-worn accelerometer data (Actigraph GT3X+, wGT3X+ and wGT3X-BT) from the Swedish CArdioPulmonary bioImage Study, SCAPIS, were included. In total, 54.5% of daily wear time was spent sedentary, 39.1% in low, 5.4% in moderate, and only 0.1% in vigorous PA. Male sex, higher education, low financial strain, born in Sweden, and sedentary/light working situation were related to higher sedentary time, but also higher levels of vigorous PA. High BMI and having multiple chronic diseases associated strongly with higher sedentary time and less time in all three PA intensities. All-year physically active commuters had an overall more active PA pattern. The proportion fulfilling current PA recommendations varied substantially (1.4% to 92.2%) depending on data handling procedures and definition used. Twenty-eight percent was defined as having an “at-risk” behavior, which included both high sedentary time and low vigorous PA. In this large population-based sample, a majority of time was spent sedentary and only a fraction in vigorous PA, with clinically important variations between subgroups. This study provides important reference material and emphasizes the importance of a comprehensive assessment of all aspects of the individual PA pattern in future research and clinical practice.
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| 43. |
- Ekerstad, Niklas, et al.
(författare)
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Acute care of severely frail elderly patients in a CGA-unit is associated with less functional decline than conventional acute care
- 2017
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Ingår i: Clinical Interventions in Aging. - : DOVE MEDICAL PRESS LTD. - 1176-9092 .- 1178-1998. ; 12, s. 1239-1248
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Tidskriftsartikel (refereegranskat)abstract
- Background: A high percentage of individuals treated in specialized acute care wards are frail and elderly. Our aim was to study whether the acute care of such patients in a comprehensive geriatric assessment (CGA) unit is superior to care in a conventional acute medical care unit when it comes to activities of daily living (ADLs), frailty, and use of municipal help services. Patients and methods: A clinical, prospective, controlled trial with two parallel groups was conducted in a large county hospital in West Sweden and included 408 frail elderly patients, age 75 or older (mean age 85.7 years; 56% female). Patients were assigned to the intervention group (n=206) or control group (n=202). Primary outcome was decline in functional activity ADLs assessed by the ADL Staircase 3 months after discharge from hospital. Secondary outcomes were degree of frailty and use of municipal help services. Results: After adjustment by regression analyses, treatment in a CGA unit was independently associated with lower risk of decline in ADLs [odds ratio (OR) 0.093; 95% confidence interval (CI) 0.052-0.164; P amp;lt; 0.0001], and with a less prevalent increase in the degree of frailty (OR 0.229; 95% CI 0.131-0.400; P amp;lt; 0.0001). When ADLs were classified into three strata (independence, instrumental ADL-dependence, and personal ADL-dependence), changes to a more dependence-associated stratum were less prevalent in the intervention group (OR 0.194; 95% CI 0.085-0.444; P=0.0001). There was no significant difference between the groups in increased use of municipal help services (OR 0.682; 95% CI 0.395-1.178; P=0.170). Conclusion: Acute care of frail elderly patients in a CGA unit was independently associated with lesser loss of functional ability and lesser increase in frailty after 3 months.
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| 44. |
- Eklöf, Vincy, 1984-, et al.
(författare)
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The prognostic role of KRAS, BRAF, PIK3CA and PTEN in colorectal cancer
- 2013
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Ingår i: British Journal of Cancer. - : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 108:10, s. 2153-2163
-
Tidskriftsartikel (refereegranskat)abstract
- Background Mutations in KRAS, BRAF, PIK3CA and PTEN expression have been in focus to predict the effect of epidermal growth factor receptor-blocking therapy in colorectal cancer (CRC). Here, information on these four aberrations was collected and combined to a Quadruple index and used to evaluate the prognostic role of these factors in CRC. Patients We analysed the mutation status in KRAS, BRAF and PIK3CA and PTEN expression in two separate CRC cohorts, Northern Sweden Health Disease Study (NSHDS; n = 197) and Colorectal Cancer in Umea Study (CRUMS; n = 414). A Quadruple index was created, where Quadruple index positivity specifies cases with any aberration in KRAS, BRAF, PIK3CA or PTEN expression. Results Quadruple index positive tumours had a worse prognosis, significant in the NSHDS but not in the CRUMS cohort (NSHDS; P = 0.003 and CRUMS; P = 0.230) in univariate analyses but significance was lost in multivariate analyses. When analysing each gene separately, only BRAF was of prognostic significance in the NSHDS cohort (multivariate HR 2.00, 95% CI: 1.16-3.43) and KRAS was of prognostic significance in the CRUMS cohort (multivariate HR 1.48, 95% CI: 1.02-2.16). Aberrations in PIK3CA and PTEN did not add significant prognostic information. Conclusions Our results suggest that establishment of molecular subgroups based on KRAS and BRAF mutation status is important and should be considered in future prognostic studies in CRC.
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| 45. |
- Ferrand-Drake Del Castillo, Gustav, 1990, et al.
(författare)
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Electrically Switchable Polymer Brushes for Protein Capture and Release in Biological Environments**
- 2022
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Ingår i: Angewandte Chemie - International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 61:22
-
Tidskriftsartikel (refereegranskat)abstract
- Interfaces functionalized with polymers are known for providing excellent resistance towards biomolecular adsorption and for their ability to bind high amounts of protein while preserving their structure. However, making an interface that switches between these two states has proven challenging and concepts to date rely on changes in the physiochemical environment, which is static in biological systems. Here we present the first interface that can be electrically switched between a high-capacity (>1 μg cm−2) multilayer protein binding state and a completely non-fouling state (no detectable adsorption). Switching is possible over multiple cycles without any regeneration. Importantly, switching works even when the interface is in direct contact with biological fluids and a buffered environment. The technology offers many applications such as zero fouling on demand, patterning or separation of proteins as well as controlled release of biologics in a physiological environment, showing high potential for future drug delivery in vivo.
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| 46. |
- Grootens, Jennine, et al.
(författare)
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Single-cell analysis reveals the KIT D816V mutation in haematopoietic stem and progenitor cells in systemic mastocytosis
- 2019
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Ingår i: EBioMedicine. - : ELSEVIER SCIENCE BV. - 2352-3964. ; 43, s. 150-158
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Tidskriftsartikel (refereegranskat)abstract
- Background: Systemic mastocytosis (SM) is a haematological disease characterised by organ infiltration by neoplastic mast cells. Almost all SM patients have a mutation in the gene encoding the tyrosine kinase receptor KIT causing a D816V substitution and autoactivation of the receptor. Mast cells and CD34(+) haematopoietic progenitors can carry the mutation: however, in which progenitor cell subset the mutation arises is unknown. We aimed to investigate the distribution of the D816V mutation in single mast cells and single haematopoietic stem and progenitor cells.Methods: Fluorescence-activated single-cell index sorting and KIT D816V mutation assessment were applied to analyse mast cells and >10,000 CD34(+) bone marrow progenitors across 10 haematopoietic progenitor subsets. In vitro assays verified cell-forming potential.Findings: We found that in SM 60-99% of the mast cells harboured the KIT D816V mutation. Despite increased frequencies of mast cells in SM patients compared with control subjects, the haematopoietic progenitor subset frequencies were comparable. Nevertheless, the mutation could be detected throughout the haematopoietic landscape of SM patients, from haematopoietic stem cells to more lineage-primed progenitors. In addition, we demonstrate that Fc epsilon RI+ bone marrow progenitors exhibit mast cell-forming potential, and we describe aberrant CD45RA expression on SM mast cells for the first time.Interpretation: The KIT D816V mutation arises in early haematopoietic stem and progenitor cells and the mutation frequency is approaching 100% in mature mast cells, which express the aberrant marker CD45RA.
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| 47. |
- Gustafsson, Sofia B, et al.
(författare)
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High tumour cannabinoid CB(1) receptor immunoreactivity negatively impacts disease-specific survival in stage II microsatellite stable colorectal cancer
- 2011
-
Ingår i: PLOS ONE. - San Francisco, CA : Public Library of Science. - 1932-6203. ; 6:8, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is good evidence in the literature that the cannabinoid system is disturbed in colorectal cancer. In the present study, we have investigated whether CB(1) receptor immunoreactive intensity (CB(1)IR intensity) is associated with disease severity and outcome. Methodology/Principal Findings: CB(1)IR was assessed in formalin-fixed, paraffin-embedded specimens collected with a consecutive intent during primary tumour surgical resection from a series of cases diagnosed with colorectal cancer. Tumour centre (n = 483) and invasive front (n = 486) CB(1)IR was scored from 0 (absent) to 3 (intense staining) and the data was analysed as a median split i.e. CB(1)IR <2 and >= 2. In microsatellite stable, but not microsatellite instable tumours (as adjudged on the basis of immunohistochemical determination of four mismatch repair proteins), there was a significant positive association of the tumour grade with the CB1IR intensity. The difference between the microsatellite stable and instable tumours for this association of CB(1)IR was related to the CpG island methylation status of the cases. Cox proportional hazards regression analyses indicated a significant contribution of CB(1)IR to disease-specific survival in the microsatellite stable tumours when adjusting for tumour stage. For the cases with stage II microsatellite stable tumours, there was a significant effect of both tumour centre and front CB(1)IR upon disease specific survival. The 5 year probabilities of event-free survival were: 8565 and 66+/-8%; tumour interior, 86+/-4% and 63+/-8% for the CB(1)IR<2 and CB(1)IR >= 2 groups, respectively. Conclusions/Significance: The level of CB(1) receptor expression in colorectal cancer is associated with the tumour grade in a manner dependent upon the degree of CpG hypermethylation. A high CB(1)IR is indicative of a poorer prognosis in stage II microsatellite stable tumour patients.
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| 48. |
- Haak, Maria, et al.
(författare)
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Home as a signification of independence and autonomy: experiences among very old Swedish people.
- 2007
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Ingår i: Scandinavian journal of occupational therapy. - : Informa UK Limited. - 1103-8128 .- 1651-2014. ; 14:1, s. 16-24
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to explore independence in the home as experienced by very old single-living people in Sweden. A grounded theory approach was used and interviews were conducted with 40 men and women aged 80-89. Data analysis revealed the core category "Home as a signification of independence" with two main categories: "Struggle for independence" and "Governing daily life". The findings showed that home is strongly linked to independence, and being independent is extremely valued. Explicit descriptions of the ageing process as an individual process of changing living conditions within the home emerged from the findings. Hence, the ageing process influences the participants' perception of themselves as independent persons. Along the ageing process the participants' view of independence changed from being independent in activity performance without help from others to experiencing independence in being able to make autonomous decisions concerning daily life at home. Consequently, there is a need to develop strategies to support very old people in staying as active and independent as possible in their own homes. In addition, since the findings highlight that independence is a complex construct, there is a need for conceptual differentiation between independence and a construct often used synonymously, namely autonomy.
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| 49. |
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| 50. |
- Haak, Maria, et al.
(författare)
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Research as an essentiality beyond one’s own competence : an interview study on frail older people's view of research
- 2024
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Ingår i: Research Involvement and Engagement. - : BioMed Central Ltd.. - 2056-7529. ; 7:1, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is an increased interest to make the voices of frail older people heard in research by actively involving them in research processes. Involving frail older people in research could, however, be perceived as challenging by researchers. To actively involve frail older people in research processes in a meaningful way, the knowledge about their own views on what research is must be widened and deepened. Methods: Individual interviews were conducted with 17 frail older men and women with former experience of participation in research studies. Qualitative data were analysed using content analysis. Results: Frail older people’s views on what research means are described through the main category; An essentiality beyond one’s own competence, which describes research as a complex process that is important for society but difficult to understand. This is described in the sub-categories; A driving force for societal development, A benefit when based on lived experience, A source of knowledge difficult to access and understand, and A respected job filled with responsibilities. Conclusion: Different views on research from the perspective of frail older people show that research is viewed as a complex yet important phenomenon to frail older people. Research was also seen as a natural part in society. Research was viewed as difficult to access and understand. Thus, researchers must train themselves to communicate research findings to the public in an understandable way. To create common understandings through information and education, researchers might be better placed to involve frail older people in a meaningful way and thereby also have the possibility to develop good working practice and relationships with those involved.
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