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- Asayama, Shinichiro, et al.
(author)
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Three institutional pathways to envision the future of the IPCC
- 2023
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In: Nature Climate Change. - : Nature Portfolio. - 1758-678X .- 1758-6798. ; 13:9, s. 877-880
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Journal article (peer-reviewed)abstract
- The IPCC has been successful at building its scientific authority, but it will require institutional reform for staying relevant to new and changing political contexts. Exploring a range of alternative future pathways for the IPCC can help guide crucial decisions about redefining its purpose.
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- Glimelius, Bengt, et al.
(author)
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A window of opportunity phase II study of enzastaurin in chemonaive patients with asymptomatic metastatic colorectal cancer
- 2010
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In: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 21:5, s. 1020-1026
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Journal article (peer-reviewed)abstract
- BACKGROUND: Preclinically, protein kinase C and AKT activation can be inhibited by enzastaurin and reduce tumor growth of colorectal cancer cells. In asymptomatic patients with metastatic colorectal cancer (mCRC), enzastaurin activity was evaluated by measuring the 6-month progression-free survival (PFS) rate in a window study design. PATIENTS AND METHODS: Chemonaive patients with asymptomatic mCRC who did not require immediate chemotherapy-induced tumor reduction received a 400-mg thrice daily loading dose of enzastaurin on day 1 of cycle 1, followed by 500 mg once daily for the remaining 28-day cycles. Progression was assessed on the basis of radiographic imaging, rise in carcinoembryonic antigen or lactate dehydrogenase (LDH) levels or by appearance of clinical symptoms. RESULTS: Twenty-eight patients received daily enzastaurin. The 6-month PFS rate was 28% [95% confidence interval (CI) 13%-45%] and median PFS was 1.9 months (95% CI 1.8-4.5 months). Twelve (43%) patients had stable disease with a median duration of 6.1 months. The survival rate at 20 months was 77% (95% CI 47%-92%). No grade 4 toxicity was reported and grade 3 toxic effects were observed in three patients with one patient showing probable drug-related elevation of liver transaminases. CONCLUSION: The window design in asymptomatic patients with mCRC can be safely applied to assess the activity and safety of novel cytostatic agents like enzastaurin.
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- Glimelius, Bengt, et al.
(author)
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Window-of-opportunity trials to evaluate clinical activity of new molecular entities in oncology
- 2011
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In: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 22:8, s. 1717-1725
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Research review (peer-reviewed)abstract
- Background: The introduction of molecular targeted agents (e. g. monoclonal antibodies or kinase inhibitors) and cancer vaccines has raised the question whether alternate clinical trial designs, including window trials, are better suited to evaluate such new molecular entities (NMEs) and improve their approval rates. In window trials, patients receive an NME for a window of time before starting standard treatment allowing the evaluation of an NME in tumors unperturbed by previous therapies. Methods: A systematic literature search was conducted to identify window trials in adult and pediatric oncology. Results: Twenty-nine window trials were identified and reviewed, 13 in pediatric and 16 in adult oncology. Most of the trials (20/29) tested cytotoxics known to have activity in other clinical situations. In contrast to trials with pretreated patients, the window trials established the antitumor activity of melphalan, topotecan, epirubicin and etoposide in untreated patients with rhabdomyosarcoma or small-cell lung cancer. In window trials with ineffective or modestly active NMEs, we found no indication of a significant negative effect on overall survival for participating patients. Conclusions: Provided close safety monitoring and careful patient selection, window trials are a safe option to investigate potential clinical activity of NMEs.
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- Ringsmuth, Andrew K., et al.
(author)
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Lessons from COVID-19 for managing transboundary climate risks and building resilience
- 2022
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In: Climate Risk Management. - : Elsevier. - 2212-0963. ; 35
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Journal article (peer-reviewed)abstract
- COVID-19 has revealed how challenging it is to manage global, systemic and compounding crises. Like COVID-19, climate change impacts, and maladaptive responses to them, have potential to disrupt societies at multiple scales via networks of trade, finance, mobility and communication, and to impact hardest on the most vulnerable. However, these complex systems can also facilitate resilience if managed effectively. This review aims to distil lessons related to the transboundary management of systemic risks from the COVID-19 experience, to inform climate change policy and resilience building. Evidence from diverse fields is synthesised to illustrate the nature of systemic risks and our evolving understanding of resilience. We describe research methods that aim to capture systemic complexity to inform better management practices and increase resil-ience to crises. Finally, we recommend specific, practical actions for improving transboundary climate risk management and resilience building. These include mapping the direct, cross-border and cross-sectoral impacts of potential climate extremes, adopting adaptive risk management strategies that embrace heterogenous decision-making and uncertainty, and taking a broader approach to resilience which elevates human wellbeing, including societal and ecological resilience.
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