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- Österblom, Henrik, et al.
(författare)
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Making the ecosystem approach operational-Can regime shifts in ecological- and governance systems facilitate the transition?
- 2010
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Ingår i: Marine Policy. - : Elsevier BV. - 0308-597X .- 1872-9460. ; 34:6, s. 1290-1299
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Tidskriftsartikel (refereegranskat)abstract
- Effectively reducing cumulative impacts on marine ecosystems requires co-evolution between science, policy and practice. Here, long-term social-ecological changes in the Baltic Sea are described, illustrating how the process of making the ecosystem approach operational in a large marine ecosystem can be stimulated. The existing multi-level governance institutions are specifically set up for dealing with individual sectors, but do not adequately support an operational application of the ecosystem approach. The review of ecosystem services in relation to regime shifts and resilience of the Baltic Sea sub-basins, and their driving forces, points to a number of challenges. There is however a movement towards a new governance regime. Bottom-up pilot initiatives can lead to a diffusion of innovation within the existing governance framework. Top-down, enabling EU legislation, can help stimulating innovations and re-organizing governance structures at drainage basin level to the Baltic Sea catchment as a whole. Experimentation and innovation at local to the regional levels is critical for a transition to ecosystem-based management. Establishing science-based learning platforms at sub-basin scales could facilitate this process.
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- Malmström, Per-Uno, et al.
(författare)
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AdCD40L immunogene therapy for bladder carcinoma--the first phase I/IIa trial
- 2010
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Ingår i: Clinical Cancer Research. - : American Association for Cancer Research. - 1078-0432 .- 1557-3265. ; 16:12, s. 3279-3287
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Immunotherapy with Bacillus Calmette-Guerin (BCG) instillation is recommended for high-risk, non-muscle invasive bladder cancer. Bacillus Calmette-Guerin is not effective in advanced tumors, and better alternatives are warranted. Immunostimulating gene therapy with adenoviral vectors expressing CD40 ligand (AdCD40L) has shown efficacy in tumor models. CD40 ligand stimulates systemic immunity and may be effective in local and invasive human disease.EXPERIMENTAL DESIGN: Patients with invasive bladder cancer scheduled for cystectomy or patients with T(a) tumors were enrolled in a phase I/IIa trial. Patients were treated with three cycles of intrabladder Clorpactin WCS-90 prewash, followed by AdCD40L instillation 1 week apart. Safety, gene transfer, immune effects, and antitumor responses were monitored.RESULTS: All eight recruited patients were treated as scheduled, and therapy was well tolerated. The main adverse effect was transient local pain during prewash. Postoperatively, urinary tract infections and one case of late septicemia with elevated potassium were reported. No adverse events were ascribed to vector therapy. Gene transfer was detected in biopsies, and bladders were heavily infiltrated with T cells. The effector marker IFN-gamma increased in biopsies, whereas levels of circulating T regulatory cells were reduced. Histologic evaluation indicated that AdCD40L therapy reduced the load of malignant cells.CONCLUSIONS: To our knowledge, this is the first report on immunogene therapy in bladder cancer and the first using AdCD40L in vivo. Local AdCD40L gene therapy was safe, boosted immune activation, and should be further evaluated as a single or an adjuvant therapy for urothelial malignancies.
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- Russell, B., et al.
(författare)
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Risk of bladder cancer death in patients younger than 50 with non-muscle-invasive and muscle-invasive bladder cancer
- 2022
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Ingår i: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 56:1, s. 27-33
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Tidskriftsartikel (refereegranskat)abstract
- Introduction and objectives Bladder cancer is primarily a disease of older age and little is known about the differences between patients diagnosed with bladder cancer at a younger versus older age. Our objectives were to compare bladder cancer specific survival in patients aged Materials and methods The Swedish bladder cancer database provided data on patient demographics, clinical characteristics and treatments for this observational study. Cox proportional hazard regression models were adjusted for appropriate variables. All analyses were stratified by disease stage (non-muscle-invasive bladder cancer and muscle-invasive bladder cancer. Furthermore, we compared the frequency of lower urinary tract infections within 24 months prior to bladder cancer diagnosis by sex and age groups. Results The study included 15,452 newly-diagnosed BC patients (1997-2014); 1,207 (8%) patients were <50 whilst 14,245 (92%) were aged 50-70. Patients aged <50 at diagnosis were at a decreased risk of bladder cancer death (HR = 0.82, 95%CI: 0.68-0.99) compared to those aged 50-70. When stratified by non-muscle-invasive and muscle-invasive bladder cancer, this association remained in non-muscle-invasive patients only (<50, HR = 0.43, 95% CI: 0.28-0.64). The frequency of lower urinary tract infection diagnoses did not differ between younger and older patients in either men or women. Conclusions Patients diagnosed with non-muscle-invasive bladder cancer when aged <50 are at decreased risk of bladder cancer-specific death when compared to their older (50-70) counterparts. These observations raise relevant research questions about age-related differences in diagnostic procedures, clinical decision-making and, not least, potential differences in tumour biology.
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