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- Abe, O, et al.
(författare)
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Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
- 2005
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Ingår i: The Lancet. - 1474-547X. ; 365:9472, s. 1687-1717
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Tidskriftsartikel (refereegranskat)abstract
- Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxombicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modem aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50-69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0 . 0001 for recurrence, 2p<0 . 00001 for breast cancer mortality) more effective than CMF chemotherapy. Few women of age 70 years or older entered these chemotherapy trials. For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50-69, &GE; 70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0 . 00001 for recurrence, 2p=0 . 01 for breast cancer mortality) more effective than just 1-2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0-4 and 5-14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis. These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1-2 years of tamoxifen versus none (33 000); and about 5 years versus 1-2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age <50 years) and 20% (age 50-69 years) from such chemotherapy were followed by a further reduction of 31% from tamoxifen in the risks that remain, the final mortality reductions would be 57% and 45%, respectively (and, the trial results could well have been somewhat stronger if there had been full compliance with the allocated treatments). Overall survival would be comparably improved, since these treatments have relatively small effects on mortality from the aggregate of all other causes. Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
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- Bengtsson, Beatrice
(författare)
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Frame dynamics and stakeholders in risk governance
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The EU governance of food safety and GM food and feed has gone through significant changes since the BSE crisis and food scares during the 1990s. This work focuses on one particular new feature; the role of stakeholders representing the food chain: biotech associations, farmer organizations, food and feed processors, consumer organizations and environmental NGOs. These stakeholders are not merely lobbyists exerting influence on EU institutions; they are knowledge producers with a certain expertise who participate within the European Food Safety Authority (EFSA) and the European Commission’s Directorate General for Health and Consumers (DG SANCO) in order to improve risk assessment as well as risk management. This study uses an interpretive approach to governance and expertise. Governance occurs in a larger system of policy discourses and architectures of meaning through which – in turn – policy options achieve meaning, are expressed, clash and compete with each other. Governance is constantly negotiated and framed, and its boundaries drawn by the various institutions and actors involved. This thesis analyses frames that are involved in the food safety governance of GMOs in the EU. Frames are understood as ideas, structures of argumentation, and the underlying rationality behind governance. Particular emphasis is placed on deliberative rationality, stakeholder participation, and how stakeholders compete to influence policy and establish themselves as legitimate experts by framing activities within a policy debate. Empirically, this thesis draws on GMO issues such as cultivation, the approval process and Environmental Risk Assessment Guidance. The policy dispute mainly explored is asynchronous authorization and zero tolerance policy. This debate contains a wide range of arguments that relate to the global trade of GMOs, feed imports, socio-economic risks, environmental contamination and consumer protection. The thesis is based on extensive research of documentary sources from policymakers and stakeholders, interviews with elite actors in Brussels and Sweden, as well as observations in the field. My conclusion is that a new governance rationality has taken hold in DG SANCO and EFSA; a deliberative rationality by which policymakers actively and innovatively engage with stakeholders and encourage them to contribute with knowledge for policy advice, risk assessment, management and process development. Yet this rationality is geared towards participation and appears in the shadow of hierarchy, meaning that participatory exercises are facilitated and firmly controlled by the policymakers themselves. It is clear that administrative rationality remains in a dominant position: GMOs are governed by ‘hard law’ in a multi-level political system that subordinates economic rationality, thereby hindering GMO market expansion in the EU. I also conclude that intertextual spinning and intertextual proximity in frames are particular important to influence policy outcomes. These enable stakeholders to become legitimate experts and influence policy response and legislative change. This is a process where data is shared, processed and spinned between public and private actors to engender its status as legitimate expertise, not interest-based claims. By such means was the problem definition in the debate on asynchronous authorization and zero tolerance policy reframed from safety to security. Overall, this work thus furthers the understanding about frames as an agenda-setting tool, and framing as influence. Even though this thesis addresses the GMO post-implementation phase, it shows that framing conflicts in the EU food safety domain are still fierce. Power struggles are ongoing, and the last boundary is far from being drawn.
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- Bengtsson, Daniel, 1975-, et al.
(författare)
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Corticotroph Pituitary Carcinoma in a Patient With Lynch Syndrome (LS) and Pituitary Tumors in a Nationwide LS Cohort
- 2017
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : OXFORD UNIV PRESS INC. - 0021-972X .- 1945-7197. ; 102:11, s. 3928-3932
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Tidskriftsartikel (refereegranskat)abstract
- Context: Lynch syndrome (LS) is a cancer-predisposing syndrome caused by germline mutations in genes involved in DNA mismatch repair (MMR). Patients are at high risk for several types of cancer, but pituitary tumors have not previously been reported. Case: A 51-year-old man with LS (MSH2 mutation) and a history of colon carcinoma presented with severe Cushing disease and a locally aggressive pituitary tumor. The tumor harbored a mutation consistent with the patients germline mutation and displayed defect MMR function. Sixteen months later, the tumor had developed into a carcinoma with widespread liver metastases. The patient prompted us to perform a nationwide study in LS. Nationwide Study: A diagnosis consistent with a pituitary tumor was sought for in the Swedish National Patient Registry. In 910 patients with LS, representing all known cases in Sweden, another two clinically relevant pituitary tumors were found: an invasive nonsecreting macroadenoma and a microprolactinoma (i.e., in total three tumors vs. one expected). Conclusion: Germline mutations in MMR genes may contribute to the development and/or the clinical course of pituitary tumors. Because tumors with MMR mutations are susceptible to treatment with immune checkpoint inhibitors, we suggest to actively ask for a family history of LS in the workup of patients with aggressive pituitary tumors.
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- Bengtsson, Hans, et al.
(författare)
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Negative emotionality and peer status : Evidence for bidirectional longitudinal influences during the elementary school years
- 2022
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Ingår i: School Psychology International. - : SAGE Publications. - 0143-0343 .- 1461-7374. ; 43:1, s. 88-105
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Tidskriftsartikel (refereegranskat)abstract
- Prior research indicates that high negative emotionality in combination with low peer status is conducive of clinically identified problems in childhood. This three-wave longitudinal study examined how negative emotionality and peer status are linked over time in middle and late childhood. Participants were recruited from second grade (n = 90, mean age = 8.85) and fourth grade (n = 119, mean age = 10.81) and were followed across a period of 2 years. Cross-lagged structural models examining concurrent and longitudinal associations between teacher-reported negative emotionality and peer ratings of likability were analyzed separately for externalizing emotion (anger) and internalizing emotion (sadness and fear). Both analyses provided support for a conceptual model in which high negative emotionality lowers peer status, and low peer status, in turn, through a feedback loop, increases negative emotionality over time. Bidirectional influences are interpreted as reflecting a transactional process involving the effects of negative emotionality on social behavior. The findings highlight the need for active efforts to help children with high negative emotionality gain acceptance from classmates.
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- Blasiak, Robert, et al.
(författare)
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Evolving Perspectives of Stewardship in the Seafood Industry
- 2021
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Ingår i: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Humanity has never benefited more from the ocean as a source of food, livelihoods, and well-being, yet on a global scale this has been accompanied by trajectories of degradation and persistent inequity. Awareness of this has spurred policymakers to develop an expanding network of ocean governance instruments, catalyzed civil society pressure on the public and private sector, and motivated engagement by the general public as consumers and constituents. Among local communities, diverse examples of stewardship have rested on the foundation of care, knowledge and agency. But does an analog for stewardship exist in the context of globally active multinational corporations? Here, we consider the seafood industry and its efforts to navigate this new reality through private governance. We examine paradigmatic events in the history of the sustainable seafood movement, from seafood boycotts in the 1970s through to the emergence of certification measures, benchmarks, and diverse voluntary environmental programs. We note four dimensions of stewardship in which efforts by actors within the seafood industry have aligned with theoretical concepts of stewardship, which we describe as (1) moving beyond compliance, (2) taking a systems perspective, (3) living with uncertainty, and (4) understanding humans as embedded elements of the biosphere. In conclusion, we identify emerging stewardship challenges for the seafood industry and suggest the urgent need to embrace a broader notion of ocean stewardship that extends beyond seafood.
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- Nilsson, R. Henrik, 1976, et al.
(författare)
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Improving ITS sequence data for identification of plant pathogenic fungi
- 2014
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Ingår i: Fungal Diversity. - : Springer Science and Business Media LLC. - 1560-2745 .- 1878-9129. ; 67:1, s. 11-19
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Tidskriftsartikel (refereegranskat)abstract
- Plant pathogenic fungi are a large and diverse assemblage of eukaryotes with substantial impacts on natural ecosystems and human endeavours. These taxa often have complex and poorly understood life cycles, lack observable, discriminatory morphological characters, and may not be amenable to in vitro culturing. As a result, species identification is frequently difficult. Molecular (DNA sequence) data have emerged as crucial information for the taxonomic identification of plant pathogenic fungi, with the nuclear ribosomal internal transcribed spacer (ITS) region being the most popular marker. However, international nucleotide sequence databases are accumulating numerous sequences of compromised or low-resolution taxonomic annotations and substandard technical quality, making their use in the molecular identification of plant pathogenic fungi problematic. Here we report on a concerted effort to identify high-quality reference sequences for various plant pathogenic fungi and to re-annotate incorrectly or insufficiently annotated public ITS sequences from these fungal lineages. A third objective was to enrich the sequences with geographical and ecological metadata. The results – a total of 31,954 changes – are incorporated in and made available through the UNITE database for molecular identification of fungi (http://unite.ut.ee), including standalone FASTA files of sequence data for local BLAST searches, use in the next-generation sequencing analysis platforms QIIME and mothur, and related applications. The present initiative is just a beginning to cover the wide spectrum of plant pathogenic fungi, and we invite all researchers with pertinent expertise to join the annotation effort.
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