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- Mattsson, Niklas, 1979, et al.
(författare)
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CSF biomarker variability in the Alzheimer's Association quality control program
- 2013
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Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 9:3, s. 251-261
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Tidskriftsartikel (refereegranskat)abstract
- Background The cerebrospinal fluid (CSF) biomarkers amyloid beta 1–42, total tau, and phosphorylated tau are used increasingly for Alzheimer's disease (AD) research and patient management. However, there are large variations in biomarker measurements among and within laboratories. Methods Data from the first nine rounds of the Alzheimer's Association quality control program was used to define the extent and sources of analytical variability. In each round, three CSF samples prepared at the Clinical Neurochemistry Laboratory (Mölndal, Sweden) were analyzed by single-analyte enzyme-linked immunosorbent assay (ELISA), a multiplexing xMAP assay, or an immunoassay with electrochemoluminescence detection. Results A total of 84 laboratories participated. Coefficients of variation (CVs) between laboratories were around 20% to 30%; within-run CVs, less than 5% to 10%; and longitudinal within-laboratory CVs, 5% to 19%. Interestingly, longitudinal within-laboratory CV differed between biomarkers at individual laboratories, suggesting that a component of it was assay dependent. Variability between kit lots and between laboratories both had a major influence on amyloid beta 1–42 measurements, but for total tau and phosphorylated tau, between-kit lot effects were much less than between-laboratory effects. Despite the measurement variability, the between-laboratory consistency in classification of samples (using prehoc-derived cutoffs for AD) was high (>90% in 15 of 18 samples for ELISA and in 12 of 18 samples for xMAP). Conclusions The overall variability remains too high to allow assignment of universal biomarker cutoff values for a specific intended use. Each laboratory must ensure longitudinal stability in its measurements and use internally qualified cutoff levels. Further standardization of laboratory procedures and improvement of kit performance will likely increase the usefulness of CSF AD biomarkers for researchers and clinicians.
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| 3. |
- Bul, Meelan, et al.
(författare)
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Active Surveillance for Low-Risk Prostate Cancer Worldwide: The PRIAS Study
- 2013
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Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 63:4, s. 597-603
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Tidskriftsartikel (refereegranskat)abstract
- Background: Overdiagnosis and subsequent overtreatment are important side effects of screening for, and early detection of, prostate cancer (PCa). Active surveillance (AS) is of growing interest as an alternative to radical treatment of low-risk PCa. Objective: To update our experience in the largest worldwide prospective AS cohort. Design, setting, and participants: Eligible patients had clinical stage T1/T2 PCa, prostate-specific antigen (PSA) <= 10 ng/ml, PSA density <0.2 ng/ml per milliliter, one or two positive biopsy cores, and Gleason score <= 6. PSA was measured every 3-6 mo, and volume-based repeat biopsies were scheduled after 1, 4, and 7 yr. Reclassification was defined as more than two positive cores or Gleason >6 at repeat biopsy. Recommendation for treatment was triggered in case of PSA doubling time <3 yr or reclassification. Outcome measurements and statistical analysis: Multivariate regression analysis was used to evaluate predictors for reclassification at repeat biopsy. Active therapy-free survival (ATFS) was assessed with a Kaplan-Meier analysis, and Cox regression was used to evaluate the association of clinical characteristics with active therapy over time. Results and limitations: In total, 2494 patients were included and followed for a median of 1.6 yr. One or more repeat biopsies were performed in 1480 men, of whom 415 men (28%) showed reclassification. Compliance with the first repeat biopsy was estimated to be 81%. During follow-up, 527 patients (21.1%) underwent active therapy. ATFS at 2 yr was 77.3%. The strongest predictors for reclassification and switching to deferred treatment were the number of positive cores (two cores compared with one core) and PSA density. The disease-specific survival rate was 100%. Follow-up was too short to draw definitive conclusions about the safety of AS. Conclusions: Our short-term data support AS as a feasible strategy to reduce overtreatment. Clinical characteristics and PSA kinetics during follow-up can be used for risk stratification. Strict monitoring is even more essential in men with high-risk features to enable timely recognition of potentially aggressive disease and offer curative intervention. Limitations of using surrogate end points and markers in AS should be recognized.
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- Zhao, R., et al.
(författare)
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Cloud partitioning of isocyanic acid (HNCO) and evidence of secondary source of HNCO in ambient air
- 2014
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Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 41:19, s. 6962-6969
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Tidskriftsartikel (refereegranskat)abstract
- Although isocyanic acid (HNCO) may cause a variety of health issues via protein carbamylation and has been proposed as a key compound in smoke-related health issues, our understanding of the atmospheric sources and fate of this toxic compound is currently incomplete. To address these issues, a field study was conducted at Mount Soledad, La Jolla, CA, to investigate partitioning of HNCO to clouds and fogs using an Acetate Chemical Ionization Mass Spectrometer coupled to a ground-based counterflow virtual impactor. The first field evidence of cloud partitioning of HNCO is presented, demonstrating that HNCO is dissolved in cloudwater more efficiently than expected based on the effective Henry's law solubility. The measurements also indicate evidence for a secondary, photochemical source of HNCO in ambient air at this site.
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