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| 15. |
- Nodin, Björn, et al.
(författare)
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Clinicopathological correlates and prognostic significance of KRAS mutation status in a pooled prospective cohort of epithelial ovarian cancer
- 2013
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Ingår i: Diagnostic Pathology. - : Springer Science and Business Media LLC. - 1746-1596. ; 8, s. 106-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Activating KRAS mutations are common in ovarian carcinomas of low histological grade, less advanced clinical stage and mucinous histological subtype, and form part of the distinct molecular alterations associated with type I tumors in the dualistic model of ovarian carcinogenesis. Here, we investigated the occurrence, clinicopathological correlates and prognostic significance of specific KRAS mutations in tumours from 153 epithelial ovarian cancer (EOC) cases from a pooled, prospective cohort. Methods: KRAS codon 12,13 and 61 mutations were analysed by pyrosequencing in tumours from 163 incident EOC cases in the Malmo Diet and Cancer Study and Malmo Preventive Project. Associations of mutational status with clinicopathological and molecular characteristics were assessed by Pearson Chi Square test. Ovarian cancer-specific survival (OCSS) according to mutational status was explored by Kaplan-Meier analysis and Cox proportional hazards modelling. KRAS-mutation status was also analysed in 28 concomitantly sampled benign-appearing fallopian tubes. Results: Seventeen (11.1%) EOC cases harboured mutations in the KRAS gene, all but one in codon 12, and one in codon 13. No KRAS mutations were found in codon 61 and all examined fallopian tubes were KRAS wild-type. KRAS mutation was significantly associated with lower grade (p = 0.001), mucinous histological subtype (p = < 0.001) and progesterone receptor expression (p = 0.035). Kaplan-Meier analysis revealed a significantly improved OCSS for patients with KRAS-mutated compared to KRAS wild-type tumours (p = 0.015). These associations were confirmed in unadjusted Cox regression analysis (HR = 2.51; 95% CI 1.17-5.42) but did not remain significant after adjustment for age, grade and clinical stage. The beneficial prognostic impact of KRAS mutation was ony evident in tumours of low-intermediate differentiation grade (p = 0.023), and in a less advanced clinical stage (p = 0.014). Moreover, KRAS mutation was associated with a significantly improved OCSS in the subgroup of endometroid carcinomas (p = 0.012). Conclusions: The results from this study confirm previously demonstrated associations of KRAS mutations with well-differentiated and mucinous ovarian carcinomas. Moreover, KRAS-mutated tumours had a significantly improved survival in unadjusted, but not adjusted, analysis. A finding that merits further study is the significant prognostic impact of KRAS mutation in endometroid carcinomas, potentially indicating that response to Ras/Raf/MEK/ERK-targeting therapies may differ by histological subtype.
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| 16. |
- Pham, Thi Bich Ngoc
(författare)
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Decentralizing hydraulic society : Actor responses to institutional arrangements in Vietnam
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Irrigation decentralization has been launched worldwide with high expectations of improved governance, efficiency, and productivity through democratic processes. However, there is widespread recognition that decentralization is, in reality, unlikely to bring about these positive outcomes. Poor implementation is widely blamed for these failures, but the current study argues that this is only partially true. Decentralization is usually treated as a technical way of power transfer that can be evaluated through quantitative indicators. Much attention goes to searching solutions to constraints during implementation while less emphasis is on understanding of contexts, processes and the consequences of institutional changes. The common approach mainly focuses on local water users’ organizations but gives insufficient attention to the cross-level interactions between involved actors, their responses to reforms, and power relationships. This approach answers the question: what should be done, but not: why do constraints/limitations occur and why are such contradictory results obtained? In this way the approach itself diffuses some of the challenges in reality and the root of problems leading to surprise consequences and failures during implementation.In this study, two irrigation systems in Vietnam were selected to examine the emerging decentralization processes, actors’ responses to the institutional changes, as well as the main options, challenges and constraints to decentralization. My ambition is also to further understand why constraints occur and have counterproductive effects. A mixed methods approach combining qualitative and quantitative methods, and cross-case analysis are applied. The database was built systematically, based on previous experience in this field, and participatory fieldwork. Decentralization is regarded as a power-laden process involving not just local organizations, but also state agencies, local authorities at different levels, state irrigation companies (IDMCs), and farmers. The study describes how institutional arrangements for decentralization have effects on the dynamics and relations of power between actors in multi-level governance, resulting in impacts on autonomy, accountability, participation, and incentives of involved actors.The analysis shows that the legal framework and several well-intended efforts for decentralization have been launched. However, outcomes in terms of power transfer and actors’ performance are not those expected. The current institutional arrangements have created major constraints: (i) imbalanced power relations, (ii) new resource allocation mechanisms creating dependency among actors, (iii) passiveness, vested interest and privilege within state agencies and IDMCs, and (iv) free-riding behavior and distrust among farmers. Prevailing conditions defy policy intentions by finding a new version of a centralized power structure at provincial level, in which power of state agencies and IDMCs are reinforced. Unexpected effects emerge on the autonomy, accountability, participation, and incentives of all involved actors. Decentralization of irrigation systems is a complex process, not merely a technical transfer of power. It is hard to achieve even with policy in place. All the complexities and implications of irrigation need to be thoroughly considered, with the dynamics in society included. Evaluations of decentralization based on production and economic terms are not enough. Impacts of institutional arrangements on power relations between actors, on their incentives, maneuver room in multi-level governance, and ability to comprehend and influence processes, need to be assessed thoroughly. Essential roles remain for central government when irrigation management is decentralized.
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| 17. |
- Ståhl, Patrik L., et al.
(författare)
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Translational Database Selection and Multiplexed Sequence Capture for Up Front Filtering of Reliable Breast Cancer Biomarker Candidates
- 2011
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:6, s. e20794-
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Tidskriftsartikel (refereegranskat)abstract
- Biomarker identification is of utmost importance for the development of novel diagnostics and therapeutics. Here we make use of a translational database selection strategy, utilizing data from the Human Protein Atlas (HPA) on differentially expressed protein patterns in healthy and breast cancer tissues as a means to filter out potential biomarkers for underlying genetic causatives of the disease. DNA was isolated from ten breast cancer biopsies, and the protein coding and flanking non-coding genomic regions corresponding to the selected proteins were extracted in a multiplexed format from the samples using a single DNA sequence capture array. Deep sequencing revealed an even enrichment of the multiplexed samples and a great variation of genetic alterations in the tumors of the sampled individuals. Benefiting from the upstream filtering method, the final set of biomarker candidates could be completely verified through bidirectional Sanger sequencing, revealing a 40 percent false positive rate despite high read coverage. Of the variants encountered in translated regions, nine novel non-synonymous variations were identified and verified, two of which were present in more than one of the ten tumor samples.
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| 20. |
- Turner, Christopher, et al.
(författare)
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Staple crops and Urban- Periurban Agriculture
- 2014
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Ingår i: Urban and periurban farming in low income countries – challenges and knowledge gaps. - 9789157692290 ; 4, s. 47-51
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Bokkapitel (refereegranskat)
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