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- Hamfjord, J., et al.
(författare)
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Total circulating cell-free DNA as a prognostic biomarker in metastatic colorectal cancer before first-line oxaliplatin-based chemotherapy
- 2019
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Ingår i: Annals of Oncology. - : Oxford University Press. - 0923-7534 .- 1569-8041. ; 30:7, s. 1088-1095
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Tidskriftsartikel (refereegranskat)abstract
- Background Metastatic colorectal cancer (mCRC) is a heterogeneous disease where prognosis is dependent both on tumor biology and host factors. Total circulating cell-free DNA (cfDNA) has shown to harbor prognostic information in mCRC, although less is known about the biological correlates of cfDNA levels in this patient group. The primary objective was to evaluate the prognostic value of pretreatment cfDNA in patients receiving the first-line oxaliplatin-based chemotherapy for mCRC, by using a predefined upper limit of normal (ULN) from a cohort of presumed healthy individuals. The secondary objective was to model cfDNA levels as a function of predefined tumor and host factors. Patients and methods This was a retrospective post hoc study based on a prospective multicenter phase III trial, the NORDIC-VII study. DNA was purified from 547 plasma samples and cfDNA quantified by a droplet digital PCR assay (B2M, PPIA) with controls for lymphocyte contamination. Main clinical end point was overall survival (OS). Results cfDNA was quantified in 493 patients, 54 were excluded mainly due to lymphocyte contamination. Median cfDNA level was 7673 alleles/ml (1050-1645000) for B2M and 5959 alleles/ml (555-854167) for PPIA. High cfDNA levels were associated with impaired outcome; median OS of 16.6months for levels above ULN and 25.9months for levels below ULN (hazard ratio = 1.83, 95% confidence interval 1.51-2.21, P<0.001). The result was confirmed in multivariate OS analysis adjusting for established clinicopathological characteristics. A linear regression model predicted cfDNA levels from sum of longest tumor diameters by RECIST, the presence of liver metastases and systemic inflammatory response as measured by interleukin 6 (F(6, 357) = 62.7, P<0.001). Conclusion cfDNA holds promise as a minimally invasive and clinically relevant prognostic biomarker in mCRC before initiating first-line oxaliplatin-based chemotherapy and may be a complex entity associated with tumor burden, liver metastases and systemic inflammatory response. Trial registration ClinicalTrials.gov, NCT00145314.
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- Aguado, D. S., et al.
(författare)
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The Fifteenth Data Release of the Sloan Digital Sky Surveys : First Release of MaNGA-derived Quantities, Data Visualization Tools, and Stellar Library
- 2019
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Ingår i: Astrophysical Journal Supplement Series. - : Institute of Physics Publishing (IOPP). - 0067-0049 .- 1538-4365. ; 240:2
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Tidskriftsartikel (refereegranskat)abstract
- Twenty years have passed since first light for the Sloan Digital Sky Survey (SDSS). Here, we release data taken by the fourth phase of SDSS (SDSS-IV) across its first three years of operation (2014 July-2017 July). This is the third data release for SDSS-IV, and the 15th from SDSS (Data Release Fifteen; DR15). New data come from MaNGA-we release 4824 data cubes, as well as the first stellar spectra in the MaNGA Stellar Library (MaStar), the first set of survey-supported analysis products (e.g., stellar and gas kinematics, emission-line and other maps) from the MaNGA Data Analysis Pipeline, and a new data visualization and access tool we call "Marvin." The next data release, DR16, will include new data from both APOGEE-2 and eBOSS; those surveys release no new data here, but we document updates and corrections to their data processing pipelines. The release is cumulative; it also includes the most recent reductions and calibrations of all data taken by SDSS since first light. In this paper, we describe the location and format of the data and tools and cite technical references describing how it was obtained and processed. The SDSS website (www.sdss.org) has also been updated, providing links to data downloads, tutorials, and examples of data use. Although SDSS-IV will continue to collect astronomical data until 2020, and will be followed by SDSS-V (2020-2025), we end this paper by describing plans to ensure the sustainability of the SDSS data archive for many years beyond the collection of data.
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- Cavalli, F., et al.
(författare)
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A European aerosol phenomenology-4 : Harmonized concentrations of carbonaceous aerosol at 10 regional background sites across Europe
- 2016
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Ingår i: Atmospheric Environment. - : Elsevier BV. - 1352-2310 .- 1873-2844. ; 144, s. 133-145
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Tidskriftsartikel (refereegranskat)abstract
- Although particulate organic and elemental carbon (OC and EC) are important constituents of the suspended atmospheric particulate matter (PM), measurements of OC and EC are much less common and More uncertain than measurements of e.g. the ionic components of PM. In the framework of atmospheric research infrastructures supported by the European Union, actions have been undertaken to determine and mitigate sampling artefacts, and assess the comparability of OC and EC data obtained in a network of 10 atmospheric observatories across Europe. Positive sampling artefacts (from 0:4 to 2.8 mu g C/m(3)) and analytical discrepancies (between -50% and +40% for the EC/TC ratio) have been taken into account to generate a robust data set, from which we established the phenomenology of carbonaceous aerosols at regional background sites in Europe. Across the network, TC and EC annual average concentrations range from 0.4 to 9 mu g C/m(3), and from 0.1 to 2 mu g C/m(3), respectively. TC/PM10 annual mean ratios range from 0.11 at a Mediterranean site to 0.34 at the most polluted continental site, and TC/PM2.5 ratios are slightly greater at all sites (0.15-0.42). EC/TC annual mean ratios range from 0.10 to 0.22, and do not depend much on PM concentration levels, especially in winter. Seasonal variations in PM and TC concentrations, and in TC/PM and EC/TC ratios, differ across the network, which can be explained by seasonal changes in PM source contributions at some sites.
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- Donahue, N. M., et al.
(författare)
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Aging of biogenic secondary organic aerosol via gas-phase OH radical reactions
- 2012
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 109:34, s. 13503-13508
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Tidskriftsartikel (refereegranskat)abstract
- The Multiple Chamber Aerosol Chemical Aging Study (MUCHACHAS) tested the hypothesis that hydroxyl radical (OH) aging significantly increases the concentration of first-generation biogenic secondary organic aerosol (SOA). OH is the dominant atmospheric oxidant, and MUCHACHAS employed environmental chambers of very different designs, using multiple OH sources to explore a range of chemical conditions and potential sources of systematic error. We isolated the effect of OH aging, confirming our hypothesis while observing corresponding changes in SOA properties. The mass increases are consistent with an existing gap between global SOA sources and those predicted in models, and can be described by a mechanism suitable for implementation in those models.
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- Emery, C A, et al.
(författare)
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OARSI Clinical Trials Recommendations: Design and conduct of clinical trials for primary prevention of osteoarthritis by joint injury prevention in sport and recreation.
- 2015
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 23:5, s. 815-825
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Forskningsöversikt (refereegranskat)abstract
- The risk of post-traumatic osteoarthritis (PTOA) substantially increases following joint injury. Research efforts should focus on investigating the efficacy of preventative strategies in high quality randomized controlled trials (RCT). The objective of these OARSI RCT recommendations is to inform the design, conduct and analytical approaches to RCTs evaluating the preventative effect of joint injury prevention strategies. Recommendations regarding the design, conduct, and reporting of RCTs evaluating injury prevention interventions were established based on the consensus of nine researchers internationally with expertise in epidemiology, injury prevention and/or osteoarthritis (OA). Input and resultant consensus was established through teleconference, face to face and email correspondence over a 1 year period. Recommendations for injury prevention RCTs include context specific considerations regarding the research question, research design, study participants, randomization, baseline characteristics, intervention, outcome measurement, analysis, implementation, cost evaluation, reporting and future considerations including the impact on development of PTOA. Methodological recommendations for injury prevention RCTs are critical to informing evidence-based practice and policy decisions in health care, public health and the community. Recommendations regarding the interpretation and conduct of injury prevention RCTs will inform the highest level of evidence in the field. These recommendations will facilitate between study comparisons to inform best practice in injury prevention that will have the greatest public health impact.
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- Glimelius, Bengt, et al.
(författare)
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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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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 21:5, s. 1020-1026
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Tidskriftsartikel (refereegranskat)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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