Indirect immunofluorescence (IIF) on human epithelial (HEp-2) cells is considered as the gold standard screening method for the detection of antinuclear autoantibodies (ANA). However, in terms of automation and standardization, it has not been able to keep pace with most other analytical techniques used in diagnostic laboratories. Although there are already some automation solutions for IIF incubation in the market, the automation of result evaluation is still in its infancy. Therefore, the EUROPattern Suite has been developed as a comprehensive automated processing and interpretation system for standardized and efficient ANA detection by HEp-2 cell-based IIF. In this study, the automated pattern recognition was compared to conventional visual interpretation in a total of 351 sera. In the discrimination of positive from negative samples, concordant results between visual and automated evaluation were obtained for 349 sera (99.4%, kappa = 0.984). The system missed out none of the 272 antibody-positive samples and identified 77 out of 79 visually negative samples (analytical sensitivity/specificity: 100%/97.5%). Moreover, 94.0% of all main antibody patterns were recognized correctly by the software. Owing to its performance characteristics, EUROPattern enables fast, objective, and economic IIF ANA analysis and has the potential to reduce intra- and interlaboratory variability.

No abstract

Antinuclear autoantibodies (ANA) are highly informative biomarkers in autoimmune diagnostics. The increasing demand for effective test systems, however, has led to the development of a confusingly large variety of different platforms. One of them, the indirect immunofluorescence (IIF), is regarded as the common gold standard for ANA screening, as described in a position statement by the American College of Rheumatology in 2009. Technological solutions have been developed aimed at standardization and automation of IIF to overcome methodological limitations and subjective bias in IIF interpretation. In this review, we present the EUROPattern Suite, a system for computer-aided immunofluorescence microscopy (CAIFM) including automated acquisition of digital images and evaluation of IIF results. The system was originally designed for ANA diagnostics on human epithelial cells, but its applications have been extended with the latest system update version 1.5 to the analysis of antineutrophil cytoplasmic antibodies (ANCA) and anti-dsDNA antibodies.

Lightweight design is one of the current key drivers to reduce the energy consumption of vehicles. Design methodologies for lightweight components, strategies utilizing materials with favorable specific properties and hybrid materials are used to increase the performance of parts for automotive applications. In this paper, various forming processes to produce light parts are described. Material lightweight design is discussed, covering the manufacturing processes to produce hybrid components like fiber–metal, polymer–metal and metal–metal composites, which can be used in subsequent deep drawing or combined forming processes. Approaches to increasing the specific strength and stiffness with thermomechanical forming processes as well as the in situ control of the microstructure of such components are presented. Structure lightweight design discusses possibilities to plastically form high-strength or high-performance materials like magnesium or titanium in sheet, profile and tube forming operations. To join those materials and/or dissimilar materials, new joining by forming technologies are shown. To economically produce lightweight parts with gears or functional elements, incremental sheet-bulk metal forming is presented. As an important part property, the damage evolution during the forming operations will be discussed to enable even lighter parts through a more reliable design. New methods for predicting and tailoring the mechanical properties like strength and residual stresses will be shown. The possibilities of system lightweight design with forming technologies are presented. A combination of additive manufacturing and forming to produce highly complex parts with integrated functions will be shown. The integration of functions by a hot extrusion process for the manufacturing of shape memory alloys is presented. An in-depth understanding of the newly developed processes, methodologies and effects allows for a more accurate dimensioning of components. This facilitates a reduction in the total mass and an increasing performance of vehicle components.

Reduction of therapy-induced morbidity is an important goal for the improvement of the quality of breast cancer treatment. The introduction of sentinel lymph node biopsy (SLNB) significantly contributed to the reduction of surgery-induced morbidity in the shoulder-arm region. However, a clinically positive nodal status is still considered a contra-indication for SLNB. The current data constellation clearly shows that the clinical and also the sonographic malignancy assessment is insufficient for the accurate identification of the nodal status. A merely clinical and/or image-based appraisal of the axillary lymph node status would lead to overtreatment due to unnecessary axillary dissection in approximately 40 % of patients. In order to reduce the rate of unnecessary axillary dissection (AD), pretreatment interventional clarification is necessary to provide more detailed information about the histological condition of the lymph node. Comparing the currently available methods, fine needle aspiration (FNA) is the best in terms of cost and time requirement, practicability and complication rate. However, considering the sensitivity, it is inferior to ultrasound-guided core needle biopsy (CNB). Thus, a negative FNA outcome requires further clarification, which possibly can be performed with CNB. With a specificity of nearly 100 % and therefore a low rate of false positive cases for FNA, complete AD can be indicated by a positive FNA result. In the context of the interventional procedure, it must be stressed that FNA requires a high level of expertise on the part of both the examiner and the cytologist. The prerequisite for optimal interventional diagnostics of lymph nodes is an adequate sonographic assessment on the basis of standardized sonomorphological criteria.

Cardiovascular reactivity to mental stress is not related to pharmacologically manipulated tonic central sympathetic nervous system activity by alpha2-adrenergic agonists and antagonists. These results do not support the assumption that cardiovascular reactivity is an index of tonic central sympathetic nervous system activity.

No abstract

PurposeIndirect immunofluorescence (IIF) on the human epithelial cell-line HEp-2 (or derivatives) serves as the gold standard in antinuclear antibody (ANA) screening. IIF, and its evaluation, is a labor-intensive method, making ANA testing a major challenge for present clinical laboratories. Nowadays, several automated ANA pattern recognition systems are on the market. In the current study, the EUROPattern Suite is evaluated for its use in daily practice in a routine setting.MethodsA total of 1033 consecutive routine samples was used to screen for ANA. Results (positive/negative ANA screening, pattern identification and titer) were compared between software-generated results (EUROPattern) and visual interpretation (observer) of automatically acquired digital images.ResultsConsidering the visual interpretation as reference, a relative sensitivity of 99.3% and a relative specificity of 88.9% were obtained for negative and positive discrimination by the software (EPa). A good agreement between visual and software-based interpretation was observed with respect to pattern recognition (mean kappa: for 7 patterns: 0.7). Interestingly, EPa software distinguished more patterns per positive sample than the observer (on average 1.5 and 1.2, respectively). Finally, a concordance of 99.3% was observed within the range of 1 titer step difference between EPa and observer.ConclusionsThe ANA IIF results reported by the EPa software are in very good agreement with the results reported by the observer with respect to being negative/positive, pattern recognition and titer, making automated ANA IIF evaluation an objective and time-efficient tool for routine testing.Electronic supplementary materialThe online version of this article (10.1007/s13317-018-0108-y) contains supplementary material, which is available to authorized users.