Uncertainty of combined activity estimations

This paper discusses basic theoretical strategies used to deal with measurement uncertainties arising from different experimental situations. It attempts to indicate the most appropriate method of obtaining a reliable estimate of the quantity to be evaluated depending on the characteristics of the data available. The theoretical strategies discussed are supported by experimental detail, and the conditions and results have been taken from examples in the field of radionuclide metrology. Special care regarding the correct treatment of covariances is emphasized because of the unreliability of the results obtained if these are neglected

Uncertainty evaluation in activity measurements using ionization chambers

Pressurized re-entrant (or 4 pi) ionization chambers (ICs) connected to current-measuring electronics are used for activity measurements of photon emitting radionuclides and some beta emitters in the fields of metrology and nuclear medicine. As a secondary method, these instruments need to be calibrated with appropriate activity standards from primary or direct standardization. The use of these instruments over 50 years has been well described in numerous publications, such as the Monographie BIPM-4 and the special issue of Metrologia on radionuclide metrology (Ratel 2007 Metrologia 44 S7-16, Schrader1997 Activity Measurements With Ionization Chambers (Monographie BIPM-4) Schrader 2007 Metrologia 44 S53-66, Cox et al 2007 Measurement Modelling of the International Reference System (SIR) for Gamma-Emitting Radionuclides (Monographie BIPM-7)). The present work describes the principles of activity measurements, calibrations, and impurity corrections using pressurized ionization chambers in the first part and the uncertainty analysis illustrated with example uncertainty budgets from routine source-calibration as well as from an international reference system (SIR) measurement in the second part.

Continuous quantification of HER2 expression by microfluidic precision immunofluorescence estimates HER2 gene amplification in breast cancer.

Chromogenic immunohistochemistry (IHC) is omnipresent in cancer diagnosis, but has also been criticized for its technical limit in quantifying the level of protein expression on tissue sections, thus potentially masking clinically relevant data. Shifting from qualitative to quantitative, immunofluorescence (IF) has recently gained attention, yet the question of how precisely IF can quantify antigen expression remains unanswered, regarding in particular its technical limitations and applicability to multiple markers. Here we introduce microfluidic precision IF, which accurately quantifies the target expression level in a continuous scale based on microfluidic IF staining of standard tissue sections and low-complexity automated image analysis. We show that the level of HER2 protein expression, as continuously quantified using microfluidic precision IF in 25 breast cancer cases, including several cases with equivocal IHC result, can predict the number of HER2 gene copies as assessed by fluorescence in situ hybridization (FISH). Finally, we demonstrate that the working principle of this technology is not restricted to HER2 but can be extended to other biomarkers. We anticipate that our method has the potential of providing automated, fast and high-quality quantitative in situ biomarker data using low-cost immunofluorescence assays, as increasingly required in the era of individually tailored cancer therapy.

Dismissal of the illusion of uncertainty in the assessment of a likelihood ratio

The use of the Bayes factor (BF) or likelihood ratio as a metric to assess the probative value of forensic traces is largely supported by operational standards and recommendations in different forensic disciplines. However, the progress towards more widespread consensus about foundational principles is still fragile as it raises new problems about which views differ. It is not uncommon e.g. to encounter scientists who feel the need to compute the probability distribution of a given expression of evidential value (i.e. a BF), or to place intervals or significance probabilities on such a quantity. The article here presents arguments to show that such views involve a misconception of principles and abuse of language. The conclusion of the discussion is that, in a given case at hand, forensic scientists ought to offer to a court of justice a given single value for the BF, rather than an expression based on a distribution over a range of values.