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| 82. |
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| 83. |
- Terry, Kathryn L., et al.
(författare)
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A Prospective Evaluation of Early Detection Biomarkers for Ovarian Cancer in the European EPIC Cohort
- 2016
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Ingår i: Clinical Cancer Research. - : American Association for Cancer Research. - 1078-0432 .- 1557-3265. ; 22:18, s. 4664-4675
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: About 60% of ovarian cancers are diagnosed at late stage, when 5-year survival is less than 30% in contrast to 90% for local disease. This has prompted search for early detection biomarkers. For initial testing, specimens taken months or years before ovarian cancer diagnosis are the best source of information to evaluate earlydetection biomarkers. Here we evaluate the most promising ovarian cancer screening biomarkers in prospectively collected samples from the European Prospective Investigation into Cancer and Nutrition study. Experimental Design: We measured CA125, HE4, CA72.4, and CA15.3 in 810 invasive epithelial ovarian cancer cases and 1,939 controls. We calculated the sensitivity at 95% and 98% specificity as well as area under the receiver operator curve (C-statistic) for each marker individually and in combination. In addition, we evaluated marker performance by stage at diagnosis and time between blood draw and diagnosis. Results: We observed the best discrimination between cases and controls within 6 months of diagnosis for CA125 (C-statistic = 0.92), then HE4 (0.84), CA72.4 (0.77), and CA15.3 (0.73). Marker performance declined with longer time between blood draw and diagnosis and for earlier staged disease. However, assessment of discriminatory ability at early stage was limited by small numbers. Combinations of markers performed modestly, but significantly better than any single marker. Conclusions: CA125 remains the single best marker for the early detection of invasive epithelial ovarian cancer, but can be slightly improved by combining with other markers. Identifying novel markers for ovarian cancer will require studies including larger numbers of early-stage cases.
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| 84. |
- Uil, Taco G, et al.
(författare)
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A lentiviral vector-based adenovirus fiber-pseudotyping approach for expedited functional assessment of candidate retargeted fibers.
- 2009
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Ingår i: The journal of gene medicine. - : Wiley. - 1521-2254 .- 1099-498X. ; 11:11, s. 990-1004
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Many studies aimed at retargeting adenovirus (Ad) rationally focus on genetic modification of fiber, which is the primary receptor-binding protein of Ad. Retargeted fibers ultimately require functional validation in the viral context. METHODS: Lentiviral vectors (LV) were used to express fiber variants in cells. Infections with a fiber gene-deleted Ad vector yielded fiber-pseudotyped viruses. An enzyme-linked immunosorbent assay and slot blot-based assays probed target binding-ability of retargeted fibers. Differential treatments with an alkylating agent prior to western blot analysis allowed for examination of intra- and extracellular redox states of fibers. RESULTS: In the present study, LV-based fiber-pseudotyping of Ad is presented as an accelerated means to test new fibers. LV-mediated gene transfer yielded stable and uniform populations of fiber variant-expressing cells. These populations were found to effectively support fiber-pseudotyping of Ad. As a secondary objective of the study, we functionally assessed a chimeric fiber harboring a tumor antigen-directed single-chain antibody fragment (scFv). This fiber was shown to trimerize and achieve a degree of binding to its antigenic target. However, its capsid incorporation ability was impaired and, moreover, it was unable to confer a detectable level of target binding upon Ad. Importantly, subsequent analyses of this fiber revealed the improper folding of its scFv constituent. CONCLUSIONS: LV-based fiber-pseudotyping was established as a convenient method for testing modified fibers for functionality within Ad particles. Furthermore, a new chimeric fiber was found to be inadequate for Ad retargeting. The folding difficulties encountered for this particular fiber might be generally inherent to the use (i.e. for genetic Ad capsid incorporation) of complex, disulfide bridge-containing natural ligands.
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| 85. |
- Van Oijen, M., et al.
(författare)
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Impact of droughts on the carbon cycle in European vegetation : a probabilistic risk analysis using six vegetation models
- 2014
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Ingår i: Biogeosciences. - : Copernicus GmbH. - 1726-4170 .- 1726-4189. ; 11:22, s. 6357-6375
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Tidskriftsartikel (refereegranskat)abstract
- We analyse how climate change may alter risks posed by droughts to carbon fluxes in European ecosystems. The approach follows a recently proposed framework for risk analysis based on probability theory. In this approach, risk is quantified as the product of hazard probability and ecosystem vulnerability. The probability of a drought hazard is calculated here from the Standardized Precipitation-Evapotranspiration Index (SPEI). Vulnerability is calculated from the response to drought simulated by process-based vegetation models. We use six different models: three for generic vegetation (JSBACH, LPJmL, ORCHIDEE) and three for specific ecosystems (Scots pine forests: BASFOR; winter wheat fields: EPIC; grasslands: PASIM). The periods 1971-2000 and 2071-2100 are compared. Climate data are based on gridded observations and on output from the regional climate model REMO using the SRES A1B scenario. The risk analysis is carried out for similar to 18 000 grid cells of 0.25 x 0.25 degrees across Europe. For each grid cell, drought vulnerability and risk are quantified for five seasonal variables: net primary and ecosystem productivity (NPP, NEP), heterotrophic respiration (Rh), soil water content and evapotranspiration. In this analysis, climate change leads to increased drought risks for net primary productivity in the Mediterranean area: five of the models estimate that risk will exceed 15 %. The risks increase mainly because of greater drought probability; ecosystem vulnerability will increase to a lesser extent. Because NPP will be affected more than Rh, future carbon sequestration (NEP) will also be at risk predominantly in southern Europe, with risks exceeding 0.25 g Cm-2 d(-1) according to most models, amounting to reductions in carbon sequestration of 20 to 80 %.
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| 86. |
- Wagenaar, Kim P., et al.
(författare)
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Effectiveness of the European Society of Cardiology/Heart Failure Association website heartfailurematters.org and an e-health adjusted care pathway in patients with stable heart failure: results of the e-Vita HF randomized controlled trial
- 2019
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Ingår i: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844. ; 21:2, s. 238-246
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Tidskriftsartikel (refereegranskat)abstract
- Background Efficient incorporation of e-health in patients with heart failure (HF) may enhance health care efficiency and patient empowerment. We aimed to assess the effect on self-care of (i) the European Society of Cardiology/Heart Failure Association website on top of usual care, and (ii) an e-health adjusted care pathway leaving out in person routine HF nurse consultations in stable HF patients. Methods and results In a three-group parallel-randomized trial in stable HF patients from nine Dutch outpatient clinics, we compared two interventions ( website and an e-health adjusted care pathway) to usual care. The primary outcome was self-care measured with the European Heart Failure Self-care Behaviour Scale. Secondary outcomes were health status, mortality, and hospitalizations. In total, 450 patients were included. The mean age was 66.8 +/- 11.0 years, 74.2% were male, and 78.8% classified themselves as New York Heart Association I or II at baseline. After 3 months of follow-up, the mean score on the self-care scale was significantly higher in the groups using the website and the adjusted care pathway compared to usual care (73.5 vs. 70.8, 95% confidence interval 0.6-6.2; and 78.2 vs. 70.8, 95% confidence interval 3.8- 9.4, respectively). The effect attenuated, until no differences after 1 year between the groups. Quality of life showed a similar pattern. Other secondary outcomes did not clearly differ between the groups. Conclusions Both the website and an e-health adjusted care pathway improved self-care in HF patients on the short term, but not on the long term. Continuous updating of e-health facilities could be helpful to sustain effects.
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| 87. |
- Zaehle, S, et al.
(författare)
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Projected changes in terrestrial carbon storage in Europe under climate and land use change, 1990-2100
- 2007
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Ingår i: Ecosystems. - : Springer Science and Business Media LLC. - 1432-9840 .- 1435-0629. ; 10, s. 380-401
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Forskningsöversikt (refereegranskat)abstract
- Changes in climate and land use, caused by socio-economic changes, greenhouse gas emissions, agricultural policies and other factors, are known to affect both natural and managed ecosystems, and will likely impact on the European terrestrial carbon balance during the coming decades. This study presents a comprehensive European Union wide (EU15 plus Norway and Switzerland, EU*) assessment of potential future changes in terrestrial carbon storage considering these effects based on four illustrative IPCC-SRES storylines (A1FI, A2, B1, B2). A process-based land vegetation model (LPJ-DGVM), adapted to include a generic representation of managed ecosystems, is forced with changing fields of land-use patterns from 1901 to 2100 to assess the effect of land-use and cover changes on the terrestrial carbon balance of Europe. The uncertainty in the future carbon balance associated with the choice of a climate change scenario is assessed by forcing LPJ-DGVM with output from four different climate models (GCMs: CGCM2, CSIRO2, HadCM3, PCM2) for the same SRES storyline. Decrease in agricultural areas and afforestation leads to simulated carbon sequestration for all land-use change scenarios with an average net uptake of 17-38 Tg C/year between 1990 and 2100, corresponding to 1.9-2.9% of the EU*s CO2 emissions over the same period. Soil carbon losses resulting from climate warming reduce or even offset carbon sequestration resulting from growth enhancement induced by climate change and increasing atmospheric CO2 concentrations in the second half of the twenty-first century. Differences in future climate change projections among GCMs are the main cause for uncertainty in the cumulative European terrestrial carbon uptake of 4.4-10.1 Pg C between 1990 and 2100.
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