| 1. |
- Arver, Brita, et al.
(author)
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Bilateral Prophylactic Mastectomy in Swedish Women at High Risk of Breast Cancer: A National Survey.
- 2011
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In: Annals of surgery. - : Lippincott Williams and Wilkins; 1999. - 1528-1140 .- 0003-4932. ; 253:6, s. 1147-1154
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Journal article (peer-reviewed)abstract
- BACKGROUND/OBJECTIVE:: This study attempted a national inventory of all bilateral prophylactic mastectomies performed in Sweden between 1995 and 2005 in high-risk women without a previous breast malignancy. The primary aim was to investigate the breast cancer incidence after surgery. Secondary aims were to describe the preoperative risk assessment, operation techniques, complications, histopathological findings, and regional differences. METHODS:: Geneticists, oncologists and surgeons performing prophylactic breast surgery were asked to identify all women eligible for inclusion in their region. The medical records were reviewed in each region and the data were analyzed centrally. The BOADICEA risk assessment model was used to calculate the number of expected/prevented breast cancers during the follow-up period. RESULTS:: A total of 223 women operated on in 8 hospitals were identified. During a mean follow-up of 6.6 years, no primary breast cancer was observed compared with 12 expected cases. However, 1 woman succumbed 9 years post mastectomy to widespread adenocarcinoma of uncertain origin. Median age at operation was 40 years. A total of 58% were BRCA1/2 mutation carriers. All but 3 women underwent breast reconstruction, 208 with implants and 12 with autologous tissue. Four small, unifocal, invasive cancers and 4 ductal carcinoma in situ were found in the mastectomy specimens. The incidence of nonbreast related complications was low (3%). Implant loss due to infection/necrosis occurred in 21 women (10%) but a majority received a new implant later. In total, 64% of the women underwent at least 1unanticipated secondary operation. CONCLUSIONS:: Bilateral prophylactic mastectomy is safe and efficacious in reducing future breast cancer in asymptomatic women at high risk. Unanticipated reoperations are common. Given the small number of patients centralization seems justified.
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| 2. |
- Schmidt, Marcus, et al.
(author)
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A comprehensive analysis of human gene expression profiles identifies stromal immunoglobulin kappa C as a compatible prognostic marker in human solid tumors
- 2012
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In: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 18:9, s. 2695-2703
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Journal article (peer-reviewed)abstract
- PURPOSE:Although the central role of the immune system for tumor prognosis is generally accepted a single robust marker is not yet available.EXPERIMENTAL DESIGN:Based on ROC (receiver operating characteristic) analyses robust markers were identified from a 60 gene B-cell derived metagene and analyzed in gene expression profiles of 1810 breast cancer, 1056 non-small cell lung cancer, 513 colorectal and 426 ovarian cancer patients. Protein and RNA levels were examined in paraffin embedded tissue of 330 breast cancer patients. The cell types were identified using immunohistochemical co-staining and confocal fluorescence microscopy.RESULTS:We identified immunoglobulin kappa C (IGKC) which as a single marker is similarly predictive and prognostic as the entire B-cell metagene. IGKC was consistently associated with metastasis free survival across different molecular subtypes in node-negative breast cancer (n=965) and predicted response to anthracycline-based neoadjuvant chemotherapy (n=845) [P less than 0.001]. In addition, IGKC gene expression was prognostic in non-small cell lung cancer and colorectal cancer. No association was observed in ovarian cancer. IGKC protein expression was significantly associated with survival in paraffin embedded tissues of 330 breast cancer patients. Tumor infiltrating plasma cells were identified as the source of IGKC expressionCONCLUSION:Our findings provide IGKC as a novel diagnostic marker for risk stratification in human cancer and support concepts to exploit the humoral immune response for anti-cancer therapy. It could be validated in several independent cohorts and performed similarly well in RNA from fresh frozen as well as from paraffin tissue and on protein level by immunostaining.
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| 3. |
- Aili, Margareta, et al.
(author)
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Functional analysis of the YopE GTPase-activating protein (GAP) activity of Yersinia pseudotuberculosis
- 2006
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In: Cellular Microbiology. - : Wiley. - 1462-5814 .- 1462-5822. ; 8:6, s. 1020-1033
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Journal article (peer-reviewed)abstract
- YopE of Yersinia pseudotuberculosis inactivates three members of the small RhoGTPase family (RhoA, Rac1 and Cdc42) in vitro and mutation of a critical arginine abolishes both in vitro GTPase-activating protein (GAP) activity and cytotoxicity towards HeLa cells, and renders the pathogen avirulent in a mouse model. To understand the functional role of YopE, in vivo studies of the GAP activity in infected eukaryotic cells were conducted. Wild-type YopE inactivated Rac1 as early as 5 min after infection whereas RhoA was down regulated about 30 min after infection. No effect of YopE was found on the activation state of Cdc42 in Yersinia-infected cells. Single-amino-acid substitution mutants of YopE revealed two different phenotypes: (i) mutants with significantly lowered in vivo GAP activity towards RhoA and Rac1 displaying full virulence in mice, and (ii) avirulent mutants with wild-type in vivo GAP activity towards RhoA and Rac1. Our results show that Cdc42 is not an in vivo target for YopE and that YopE interacts preferentially with Rac1, and to a lesser extent with RhoA, during in vivo conditions. Surprisingly, we present results suggesting that these interactions are not a prerequisite to establish infection in mice. Finally, we show that avirulent yopE mutants translocate YopE in about sixfold higher amount compared with wild type. This raises the question whether YopE's primary function is to sense the level of translocation rather than being directly involved in downregulation of the host defence.
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| 4. |
- Aili, Margareta, et al.
(author)
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Regulation of Yersinia Yop-effector delivery by translocated YopE
- 2008
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In: International Journal of Medical Microbiology. - : Elsevier. - 1438-4221 .- 1618-0607. ; 298:3-4, s. 183-192
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Journal article (peer-reviewed)abstract
- The bacterial pathogen Yersinia pseudotuberculosis uses a type III secretion (T3S) system to translocate Yop effectors into eukaryotic cells. Effectors are thought to gain access to the cytosol via pores formed in the host cell plasma membrane. Translocated YopE can modulate this pore formation through its GTPase-activating protein (GAP) activity. In this study, we analysed the role of translocated YopE and all the other known Yop effectors in the regulation of effector translocation. Elevated levels of Yop effector translocation into HeLa cells occurred by YopE-defective strains, but not those defective for other Yop effectors. Only Yersinia devoid of YopK exhibits a similar hyper-translocation phenotype. Since both yopK and yopE mutants also failed to down-regulate Yop synthesis in the presence of eukaryotic cells, these data imply that translocated YopE specifically regulates subsequent effector translocation by Yersinia through at least one mechanism that involves YopK. We suggest that the GAP activity of YopE might be working as an intra-cellular probe measuring the amount of protein translocated by Yersinia during infection. This may be a general feature of T3S-associated GAP proteins, since two homologues from Pseudomonas aeruginosa, exoenzyme S (ExoS) and exoenzyme T (ExoT), can complement the hyper-translocation phenotypes of the yopE GAP mutant.
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| 5. |
- Anders, Isaksson, 1965-, et al.
(author)
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Institutional theory and contracting in venture capital : the Swedish experience
- 2004
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In: Venture Capital. - London : Taylor & Francis. - 1369-1066 .- 1464-5343. ; 6:1, s. 47-71
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Journal article (peer-reviewed)abstract
- This paper tests the tenets of institutional theory by means of an empirical study of the contractual strategies applied in the Swedish venture capital industry. Venture capitalists differ in, for example, their preferences for early or later stage investments. Some have more experience than others and some are employed by public funds while others work in non-public funds. The sector, however, was expected to be relatively homogeneous due to the small size of the industry and the cultural milieu in which it is located. This homogeneity was tested regarding the use of contractual strategies among venture capitalists in Sweden. Seventy-nine separate contractual covenants were examined in relation to distinctive sector variables, structure, experience and investment preferences. The results indicate that the greatest differences in contractual strategies occur among those with differing investment preferences. There appear to be two distinct venture capital cultures controlling contractual choices in these groups. The public and the non-public sector have limited variations in their contractual choices, although public funds employ slightly more standardized strategies. Little difference was found between the contractual choices made by experienced and inexperienced venture capitalists. The findings generally conform to the outcomes predicted by institutional theory.
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| 6. |
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| 7. |
- Andersson, Kasper G, et al.
(author)
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Revision of deposition and weathering parameters for the ingestion dose module (ECOSYS) of the ARGOS and RODOS decision support systems.
- 2011
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In: Journal of environmental radioactivity. - : Elsevier BV. - 1879-1700 .- 0265-931X.
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Journal article (peer-reviewed)abstract
- The ECOSYS model is the ingestion dose model integrated in the ARGOS and RODOS decision support systems for nuclear emergency management. The parameters used in this model have however not been updated in recent years, where the level of knowledge on various environmental processes has increased considerably. A Nordic work group has carried out a series of evaluations of the general validity of current ECOSYS default parameters. This paper specifically discusses the parameter revisions required with respect to the modelling of deposition and natural weathering of contaminants on agricultural crops, to enable the trustworthy prognostic modelling that is essential to ensure justification and optimisation of countermeasure strategies. New modelling approaches are outlined, since it was found that current ECOSYS approaches for deposition and natural weathering could lead to large prognostic errors.
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| 8. |
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| 9. |
- Antonson, Hans, et al.
(author)
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Negotiating climate change responses : Regional and local perspectives on transport and coastal zone planning in South Sweden
- 2016
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In: Land use policy. - : Elsevier BV. - 0264-8377 .- 1873-5754. ; 52, s. 297-305
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Journal article (peer-reviewed)abstract
- Putting climate change policy-integration into practice is challenged by problems of institutional misfit, due to, inter alia, deficient vertical administrative interplay. While most focus within the field of climate change research has targeted the national-local interplay, less is known about the interface of regional and local perspectives.Here, the aim is to study that interface with a specific focus on the relation between regional and local spatial planning actors, through a case-study of transport and coastal zone management in a Swedish municipality. The article is based on interviews (focus group and single in-depth) and official planning documents.The material reveals a tricky planning situation, replete with conflict. In practice, various institutional frameworks, claims and ambitions collide. The attempts to steer the local spatial planning initiatives from the regional level led to conflicts, which in turn seems to have hampered the overall work for climate change management through spatial planning. Furthermore, there are few traces of prospects of a smooth vertical institutional interplay able to support the overall aims related to integrating climate change mitigation and adaptation in spatial planning.
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