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Objective: The Paris System for Reporting Urinary Cytology considered the nuclear‐to‐cytoplasmic (N:C) ratio as the most important cytomorphological feature for detecting high‐grade urothelial carcinoma (HGUC) cells. Few quantitative studies have been conducted on other features although quantitative studies on the N:C ratio have been reported. Therefore, this study quantitatively analysed important cytomorphological features in distinguishing benign reactive cells from HGUC cells. Methods: We analysed 2866 cells from the urine of 52 patients. A digital image analyser was used to quantitatively measure the nuclear area, cell area, N:C ratio, and nuclear roundness for HGUC cells and benign reactive cells. Additionally, the diagnostic value of quantitative cytomorphological criteria in HGUC cells was evaluated by the receiver operating characteristic curve. Results: The area under the curve for the prediction of HGUC cells for all cells and the top five cells was in the following order: nuclear area (0.920 and 0.992, respectively), N:C ratio (0.849 and 0.977), cell area (0.781 and 0.920), and nuclear roundness (0.624 and 0.605). The best cutoff value of the N:C ratio to differentiate HGUC cells from benign reactive cells was 0.438, and using the N:C ratio of 0.702, the positive predictive value obtained was 100%. Conclusions: Our study indicated that nuclear area is a more important cytomorphological criterion than the N:C ratio for HGUC cell detection. Moreover, extracted data of the top five cells were more valuable than the data of all cells, which can be helpful in the routine practice and future criteria definition in urine cytology. [ABSTRACT FROM AUTHOR]

Objective: The Paris System for Reporting Urinary Cytology (TPS) is a well‐known urinary diagnostic model; however, occasional false‐positives are a problem. To address this issue, we developed an improved algorithm (IA), based on additional cytological features, for TPS diagnosis. Methods: Cytological features were evaluated in 29 hard‐to‐classify cases, including 22 malignant cases and seven benign cases, using image analysis. The optimal IA was determined using the area under the receiver operating characteristic curve as an index. Re‐evaluation was performed by applying measured values to the TPS and IA algorithms. Results: Using TPS, 12 of the 22 malignant cases were reassigned to a more appropriate category, and the remaining 10 malignant cases remained hard‐to‐classify. Two of the seven benign cases were classified as suspicious for high‐grade urothelial carcinoma, and the remaining five benign cases remained in the original category. The IA, which included nuclear area as a parameter, showed the same diagnostic sensitivity as TPS, and three of the seven benign cases were reassessed as negative. Thus, the positive and negative predictive values of the IA were higher than those of TPS (84.6% and 100% vs 75.9% and 0%). Conclusions: The newly developed IA is a practical algorithm with which to address the limitations of TPS and thus may contribute to improved diagnostic accuracy. [ABSTRACT FROM AUTHOR]

Background: Bronchoalveolar lavage (BAL) is one of the fundamental examinations for the differential diagnosis of interstitial lung diseases (ILDs), and lymphocytosis strongly indicates alternative diagnoses rather than idiopathic pulmonary fibrosis. However, the BALF lymphocytosis is observed in several ILDs. We considered that quantitative evaluation of the BALF lymphocyte nuclear morphology would be useful in the differential diagnosis of ILDs with increased BALF lymphocyte fraction.Results: One hundred and twenty-one patients with ILDs having increased BALF lymphocyte fraction were recruited (68 in the development cohort and 53 in the validation cohort). In the development cohort, BALF lymphocyte nuclei in sarcoidosis patients showed significantly smaller areas, shorter perimeters, lower radius ratios, and increased roundness than those of other ILD patients (p < 0.001 for each). Next, the fractions of lymphocytes with small areas, short perimeters, low radius ratios, and increased roundness, which were determined based on receiver operating characteristic (ROC) analyses-based thresholds, were demonstrated to be higher in sarcoidosis patients than in the other ILD patients (p < 0.001 for each). Furthermore, when we combined size-representing parameters with shape-representing parameters, the fraction of lymphocytes with small and round nuclei showed approximately 0.90 of area under the ROC curve in discriminating sarcoidosis both in the development cohort and the validation cohort.Conclusion: This study is the first to demonstrate the usefulness of quantitative parameters of BALF lymphocyte nuclear morphology as novel biomarkers for sarcoidosis. [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus is an extremely common endocrine metabolic disorder that results in chronic hyperglycemia. It has effects on various tissues of the body. Due to this increased blood glucose levels considerable cellular changes occur in oral cavity as well. This field has attracted little research. The aim of the study was to analyze the changes in morphology and cytomorphometric measurements in the buccal mucosal cells of type 2 diabetic patients. Objectives: The Objective of this study was to detect the cytological and morphological alterations of oral epithelial cells, in type 2 diabetic patients and healthy control subjects in exfoliated cytology smears, to compare the cytoplasmic diameter, nuclear diameter, and nucleus: cytoplasm ratio in type 2 diabetics and healthy control subjects and to analyze the above mentioned cellular alterations in patients with controlled and uncontrolled diabetes. Methods: Cross-sectional analysis was performed in three groups on the bases of HbA1c levels. Group 1 was uncontrolled diabetics with HbA1C ≥ 7.0%, Group 2 was well controlled diabetics with HbA1c ≤ 7.0% and Group 3 was Control healthy having HbA1C ≤ 5. 6%. Smears from normal buccal mucosa were obtained from each subject and stained with Papanicolaou method. An eyepiece micrometer was used to take mean values of ND, CyD, and N: C ratio. Fifty (50) clearly defined cells were measured in each case in a step wise manner, to evade quantifying cells once more. Comparison of Nuclear Diameter (ND), Cytoplasmic Diameter (CY D) and ratio of two Diameters (N: C) among three groups was performed by using ANOVA. TUKEY'S test for post -hoc analysis was used where required. Results: The variability in diameter of nucleus among all three sample groups showed significant p-value < 0.001.Whereas the measurement for cytoplasmic diameter between three groups was not significant (pvalue 0.178). The ratio of nuclear diameter to cytoplasmic diameter calculated was significant (p-value < 0.001). Hence it proved from the results that considerably exaggerated ND and N: C ratios were seen as the glycemic control (HbA1C) is poorer. Conclusion: The results suggested that nuclear size of buccal mucosal cells increased in type 2 diabetic patients while no change was observed in cytoplasmic dimensions. [ABSTRACT FROM AUTHOR]

For more than five years (2006–2011), the OECD/NEA/CSNI PRISME fire research program were conducted in an international framework. It dealt mainly with smoke and heat propagation mechanisms in multi-compartment fire scenarios and with the consequences of fire on targets of interest (thermal stress on electrical cables and their potential malfunction). The PRISME project included several organizations from 12 OECD/NEA member countries: Belgium (TRACTEBEL-Suez, BEL_V), Canada (AECL), Finland (STUK, VTT), France (IRSN, EdF, DGA), Germany (GRS, iBMB, BfS), Japan (JNES), Korea (KINS), Spain (CSN), Sweden (Vattenfall Ringhals), UK (HSE), The Netherlands (VROM-KFD, NRG), and USA (NRC). As PRISME project leader, the French Institut de Radioprotection et de Sûreté Nucléaire (IRSN) carried out many fire experiments in confined and mechanically ventilated compartments representative of fire scenarios in the nuclear industry. These fire tests were performed in a large-scale facility, named DIVA, including five compartments connected to an industrial ventilation network. The design of this experimental facility can quite easily be fitted for various fire scenarios of interest in nuclear area and to comply with fire hazard expertise needs. During this PRISME project, five experimental campaigns (more than 35 large-scale fire tests) were performed from early 2006 up to mid-2011, named PRISME Source (one single room), PRISME Door (two or three rooms with doorways), PRISME Leak (two rooms linked with leakages) and PRISME Integral (three and four rooms with doorways). This paper presents a general summary of the PRISME project (description of the experimental facilities, matrix of experiments, experimental instrumentation used during the fire tests, main objectives of fire experiments) and focuses on some outstanding results. The experimental outcomes obtained during this PRISME project provides a better understanding and an increase of knowledge in fire development in confined and ventilated large-scale compartments representative of nuclear area. Moreover, they also contribute to the improvement of fire modelling and constitute a huge experimental database used to validate fire safety softwares (based on zone modelling, lumped parameter approach and CFD). [ABSTRACT FROM AUTHOR]

Background: The use of oral exfoliative cytology as a diagnostic aid accentuates the need for establishing an accurate baseline, thereby enabling the comparison of abnormal oral tissue with established baseline. Aims and Objective: To detect any changes in the nuclear area (NA), cytoplasmic area (CA), and nuclear:cytoplasmic ratio (N:C ratio) values for clinically normal gingival smears in relation to age and sex of apparently healthy subjects. Materials and Methods: Gingival smears were collected from 80 (40 male, 40 female) apparently healthy subjects belonging to the age group of 0-20, 21-40, 41-60, and more than 60 years. Smear slides were fixed by using spray fixative. The smears were stained using Papanicolaou procedure. The cytoplasmic and NAs were measured using image analysis software. Statistical analysis of the data was done using one-way ANOVA with Tukey-HSD procedure and Student's t test. Results: The result showed that there was a significant difference (P<0.001) in NA, CA, and N:C in males of different age groups. There was a significant difference (P<0.001) in NA, CA, and N:C in females of different age groups. The difference in N:C between males and females was significant (P<0.001) in all the groups. The difference in NA, CA, and N:C with age irrespective of gender was significant (P<0.05). There was a significant difference (P<0.05) between males and females with respect to NA, CA, and N:C irrespective of age. Conclusion: Age-and sex-related alterations were observed in gingival smears, which could be a baseline for these variables to compare identical measurements, made on pathologic smears of oral premalignant and malignant lesions. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The present study was undertaken to analyze the impact of epigenetic alterations with a main focus on nuclear area, aneuploidy, hyperploidy, and proliferation in 70 ovarian cancer specimens. Methods: Morphometric changes and somatic chromosomal ploidy status were assessed by Feulgen spectrophotometry. DNA-hypomethylation of LINE1 repeats was analyzed by means of MethyLight PCR, and methylation levels of satellite 2 (Sat2) and satellite alpha (Satα) DNA sequences in chromosome 1 were measured by Southern blot analysis. These parameters were analyzed with regard to correlations as well as to recurrence and survival. Results: We identified a significant association between LINE1 DNA-hypomethylation and patient age (p =0.029). Furthermore, LINE1 DNA-hypomethylation was positively correlated with the nuclear area (r=0.47; p <0.001) and the proliferation index (r=0.36; p <0.001). Univariate survival analysis showed that the nuclear area and LINE1 DNA-hypomethylation were prognostic factors for overall (p =0.015 and =0.006, respectively) and progression-free survival (p =0.020 and p =0.001 respectively), the percentage of aneuploidy only for overall survival (p =0.031). Subgroup survival analyses revealed that the prognostic value of these factors is strictly confined to mucinous cancers. In serous cancers no prognostic value could be pointed out for any analyzed parameter. Multivariate analysis of the entire cohort showed that the percentage of hyperploidy was an independent prognostic parameter for overall survival (p =0.003) and LINE1 DNA-hypomethylation for progression-free survival (p =0.03). In mucinous cancers nuclear area and LINE1 DNA-hypomethylation were found to be independent predictors of progression-free and overall survival. Conclusions: In this study we identified the correlations between early cancer-associated genome DNA-hypomethylation, nuclear morphometric changes, somatic chromosomal ploidy status and the proliferation index. Prognostic relevance of nuclear area and LINE1 DNA-hypomethylation was revealed exclusively in mucinous ovarian cancers. [Copyright &y& Elsevier]

The article presents a study that assesses the primary tumors of pulmonary adenocarcinomas using image processor. It mentions that pathologists examined the nuclear factors relative to small lymphocytes' size as a standard. The study used receiver operator characteristic curve analysis and made survival curves through Kaplan-Meier method to evaluate the result. Its results show that lung adenocarcinomas were divisible into two groups revealing extremely favorable and fairly favorable prognosis.

Background: Nuclear texture analysis is a useful method to obtain quantitative information for use in prognosis of cancer. The first-order gray level statistics of a digitized light microscopic nuclear image may be influenced by variations in the image input conditions. Therefore, we have previously standardized the nuclear gray level mean value and standard deviation. However, there is a clear relation between nuclear DNA content, area, first-order statistics, and texture. For nuclei with approximately the same DNA content, the mean gray level increases with an increasing nuclear area. The aims of the present methodical work were to study: (1) whether the prognostic value of adaptive textural features varies with nuclear area, and (2) the effect of standardizing nuclear first-order statistics. Methods: Nuclei from 134 cases of ovarian cancer were grouped into intervals according to nuclear area. Adaptive features were extracted from two different image sets, i.e., standardized and non-standardized nuclear images. Results: The prognostic value of adaptive textural features varied strongly with nuclear area. A standardization of the first-order statistics significantly reduced this prognostic information. Several single features discriminated the two classes of cancer with a correct classification rate of 70%. Conclusion: Nuclei having an area between 2000–4999 pixels contained most of the class distance information between the good and poor prognosis classes of cancer. By considering the relation between nuclear area and texture, we avoided a loss of information caused by standardizing the first-order statistics and mixing data from cells having different nuclear area. [ABSTRACT FROM AUTHOR]

Ductal carcinoma in situ (DCIS) is a heterogeneous group of lesions that has been subdivided into three types: well differentiated (grade I), moderately differentiated (grade II), and poorly differentiated (grade III). Forty-five cases of DCIS were analyzed for image analysis: nuclear area, DNA ploidy, and vascularization in order to establish a more precise correlation between the histologic grade and these morphometric parameters. Our results confirm that the mean nuclear area, DNA ploidy, and microvessel density (MVD) progressively increased from DCIS grade I to DCIS grade III. The analysis of the nuclear area in relationship to DCIS grading demonstrated a progressive increase of values between grades I/II to grade III, but these data have no statistical significance. An analysis of DNA ploidy demonstrated significant differences between grades I/III (p < 0.05), but there was no statistical significance between grades I/II, grades II/III, or both (p > 0.005). The analysis of MVD was extremely significant between grades I/III (p < 0.001) and grades II/III (p < 0.001), but between grades I/II, these values showed no significant differences (p > 0.05). Based on this study, it can be concluded that image analysis techniques confirm how DCIS presents morphometric values that increase from DCIS grade I to DCIS grade III and that within this spectrum, DCIS grade III can be identified as a group of tumors presenting a large nuclear area, aneuploid DNA, and abundant vascular neogenesis, confirming that this neoplasm displays more aggressive patterns than the other two types. These criteria should justify a higher rate of tumor progression to DCIS grade III. [ABSTRACT FROM AUTHOR]

The accurate detection of malignant neoplasms whilst they are still small is recognised as one of the main factors increasing chances of survival. Neural networks have many biomedical applications and they have been applied to neoplasia but their use in oral pathology has only recently been documented. The objectives of this study were to train networks to discriminate between normal and dysplastic mucosa. Each network was trained by back propagation, internal cross validation and tested on additional data. The data were derived by analysing 348 intra-oral smears and included mean nuclear and mean cytoplasmic areas of the smears measured by image analysis. A neural network differentiated between normal/non-dysplastic mucosa and dysplastic/malignant mucosa (specificity 0.82, sensitivity 0.76). These early results suggest that integrating neural networks and image analysis, as well as investigating additional criteria, could enhance automation and accuracy of smear techniques in diagnosing oral malignancy. [ABSTRACT FROM AUTHOR]

The purpose of this study was to assess cellular proliferative activity of clinically healthy oral mucosal epithelial cells of toombak dippers and smokers by means of AgNOR counts and nuclear areas via nuclear morphometry. Smears were collected from normal-appearing mouth floor mucosa and tongue of 75 toombak dippers, 75 smokers and 50 non-tobacco users between the ages of 20 and 70 with a mean age of 36 years. AgNORs were counted in the first 50 well-fixed, nucleated squamous cells and nuclear areas were calculated via microscopic stage micrometer. Cytological atypia was ascertained in 6 tobacco users and could not be ascertained in non-tobacco users. Statistically mean AgNOR numbers per nucleus in the nontobacco users (2.45±0.30) was lower than the toombak dippers (3.081±0.39, p<0.004), and the smokers (2.715±0.39, p<0.02), and mean nuclear areas of epithelial cells of toombak dippers (6.081±0.39, p<0.009) and smokers (5.68±10.08, p<0.01) was also significantly higher than non-smokers (5.39±9.4). The mean number of nuclei having more than 3 AgNORs was 28%, 19% and 7% in toombak dippers, smokers and non-tobacco users, respectively. These findings support the view that toombak dipping and smoking are severe risk factors for oral mucosal proliferative lesions and exfoliative cytology is valid for screening of oral mucosal lesions. [ABSTRACT FROM AUTHOR]