Mitotic count in breast cancer. The influence of training on performance

Two medical laboratory histotechnologists were trained on mitotic counting for 6 months and 1 year. The training included detailed theoretical education on mitotic counts and microscopy sessions with a motivated pathologist. Most of the training time, however, was used for mitotic counts from a large collection of breast cancer samples. The progress in performance was followed by allowing the technicians to count 20 breast cancer samples several times during the training. The mean value of the mitotic counts of technician 1 varied dramatically during the early phases of training but then stabilized near the levels of technician 2, whose mean values were more constant throughout the training period. Both observers showed changes in the standard deviation and coefficient of variation in the early phases of training but later stabilized at the same level. The proportion of the counting results of the technicians within the 95% confidence limits determined by the performance of already trained, experienced technicians varied considerably at first, but then stabilized at values 0.7 and above. The study showed that training improved the performance in mitotic counting. We suggest that the training of mitotic counts provides the means to achieve economical and reproducible estimates of tumor cell proliferation.     

A multi-expert system for ranking patents: An approach based on fuzzy pay-off distributions and a TOPSIS–AHP framework

The aim of this paper is to introduce a decision support system that ranks patents based on multiple expert evaluations. The presented approach starts with the creation of three value scenarios for each considered patent by each expert. These are used for the construction of individual fuzzy pay-off distribution functions for the patent value; a consensual fuzzy pay-off distribution is then determined starting from the individual distributions. Possibilistic moments are calculated from the consensus pay-off distribution for each patent and used in ranking them with TOPSIS. It is further showed how the analytic hierarchy process (AHP) can be used to include additional decision variables into the patent selection, thus allowing for a two-tier decision making process. The system is illustrated with a numerical example and the usability of the system and the combination of methods it includes for patent portfolio selection in the real world context is discussed.     

The design and use of nuclear orientation thermometers employing54Mn and60Co nuclei in ferromagnetic hosts

The magnetic dipole interaction between the nuclear magnetic momentu and the hyperfine fieldH _hf in ferromagnetic metals leads to well-defined, evenly spaced nuclear energy levels which are accurately measurable by NMR techniques. When this is combined with the well-established anisotropic -ray emission properties of radioactive nuclei an excellent basis for absolute temperature measurement between 1 and 30 mK is obtained. Practical applications, however, require consideration of several experimental aspects. These are discussed in detail and graphs and tables are given in such a form that the data can be easily utilized. Experience gained with a nuclear orientation thermometer system employed in a nuclear refrigeration cryostat is discussed. A calibration of a pulsed copper NMR thermometer against a⁵⁴MnNi nuclear orientation thermometer is presented.     

The viscosity and some related properties of liquid3He at the melting curve between 1 and 100 mK

The viscosity of liquid ³ He has been measured along the melting curve from 1 to 100 mK by means of a vibrating wire viscometer. In the normal Fermiliquid region we find 1/T² = 1.17–3.10T, where is in P and T in K. At the transition temperature T _A = 2.6 mK a rapid decrease occurs in _n , the viscosity of the normal component. Within 0.3 mK below T _A , _n decreases to about 25% of _A, but then becomes essentially constant. In the B phase _n first decreases to 20% of _A and then seems to increase below 1.4 mK. Data on _n , the density of the normal component, are also presented in the A and B phases. The results show that viscous flow is accompanied by a flow of zero dissipation, thus proving superfluidity in the A and B phases. The viscosity data at magnetic fields up to 0.9T have been related to theoretical calculations of the energy gap of superfluid ³ He near T _A . The splitting of the A transition and the suppression of the B phase in an external field were also measured.     

How to develop and use a Bayesian Belief Network

Changes in patterns of gene induction by myeloid lineage cells following multiple exposures to endotoxin (lipopolysaccharide; LPS) is a feature of LPS tolerance. To further understand the mechanism of this phenomenon we describe studies using stably transfected Chinese hamster ovary cell lines that express human CD14 (CHO-hCD14). Using NF-kappa B activation as a measure of LPS-induced cell activation we show that a single treatment with LPS renders CHO-hCD14 cells tolerant to subsequent challenge with LPS, but not with other stimuli such as tumor necrosis factor. Tolerance may result from the induction of gene(s) that control LPS-induced signaling pathways and here we suggest that such genes may be found in the group of immediate, early response genes characterized by the protein phosphatase 3CH134. The CHO-hCD14 cell lines provide a novel model system to further explore the mechanism of endotoxin tolerance.     

Electron microscopy of postmortem autolysis of rat muscle tissue

To define the progression of ultrastructural changes in normal muscle at post mortem, rat gastrocnemius muscles were studied at various times after storage at +4 degrees C and +22 degrees C. Degeneration of the I-zone (discoid necrosis) and membranous bodies were found to be similar to that seen in muscle diseases, and lamellar formations were seen in mitochondria. At +4 degrees C there was contraction of the sarcomere which vanished in 12 h and inter-filamentous oedema appeared. Z-line degeneration was seen at 24 h and at 4 days all Z-lines had disappeared, and the H-zone showed darkening. In the same samples collapse or ruptures of the I band were seen. At 8 days the H-zones and M-lines were still discernible. In the early stages the mitochondria showed swelling and loss of matrix granules, while later they showed broken cristae and outer membranes, and flocculent densities. At 4 days rearrangement of the cristal material into long pentalaminar "needles" was seen in a few mitochondria. At 4 and 8 days membranous bodies were seen and the T-system and sarcoplasmic reticulum showed ruptures and disintegration into vesicles. The nucleus showed increasing condensation of chromatin at the periphery and clearing of the center. Polysomes and glycogen were reduced at 2 h, and has practically vanished at 24 h. At 22 degrees C the changes were the same but appeared about 4 times as quickly as at +4 degrees C.     

Incorporating Hydrologic Uncertainty in Industrial Economic Models: Implications of Extreme Rainfall Variability on Metal Mining Investments

Water balance uncertainties have long been known to lead to potential environmental hazards, but their effect on economic profitability of mines is an under-studied field of research. Historical rainfall data are analyzed using the extreme value theory (EVT) and the peak over threshold method (POT). The resulting distributions are used as inputs into a system dynamics techno-economic metal mining investment profitability model, and simulation analysis is performed. The proposed methodology incorporates rainfall extremes and uncertainty into techno-economic modeling of metal mining operations. A case study with real-life historical rainfall data was used to illustrate the relationship between hydrologic uncertainty and the economic value of a metal mining investment.

     

Morphometric grading in breast cancer: thresholds for mitotic counts

Three hundred sixty-four cases of invasive ductal breast cancer diagnosed during the years 1988 to 1991 were analyzed to determine quantitative thresholds for mitotic activity. Mitotic counts were calculated in each sample and expressed as standardized mitotic index (SMI) and mitotic activity index (MAI). Based on Kaplan-Meier curves, univariate and multivariate analysis of Cox's regression, and maximum efficiencies of ROC analysis, optimal thresholds were determined on the basis of survival and recurrence of disease. In our material, with a follow-up time of 5 years 9 months, we found two thresholds--a lower and a higher--for both SMI (17 mitoses/mm2 and 32 mitoses/mm2) and MAI (13 mitoses/10 HPF and 35 mitoses/10 HPF). The thresholds were the same in the whole material and in subgroups divided according to the patients' age and axillary lymph node status at the time of diagnosis, and tumor size. The thresholds clearly separated patients with favorable, intermediate, and unfavourable outcome of disease. In our material, the risk of breast cancer death associated with the determined thresholds (ranging from 4.7 to 3.8) clearly exceeded those of menopausal status, axillary lymph node status and tumor size. The risk of breast cancer death associated with the determined thresholds was still emphasized in the groups of premenopausal and axillary lymph node-negative patients, and with tumor size less than 2 cm in diameter (risk ratios, 11.8, 6.0, and 6.7, respectively). The results suggest that the presented quantitative thresholds could be applied in grading of invasive ductal breast cancer.