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The extension of Gompertz law's validity.

The interval 35-85 years is mostly considered as the range of Gomperz law's validity. Looking at the spectrum of causes of death for the interval 10-30 years we find that its main share is caused by various accidents independent of age. These accidents result in the increase and following plateau of the total mortality curve over the age of 15 years. When the number of deaths from age independent causes (accidents, violence, suicide, accidental falls, etc.) is subtracted from the total number of deaths the linear area begins before the age of 20 years. The linear regression of the logarithm of mortality without accidents was performed for the age interval 20-84 years for six populations (men and women in the US in 1989, in Japan in 1990 and in former Czechoslovakia in 1990). Furthermore, the mortality curves of some causes important at the interval 0-15 years were inspected. Unlike other causes, births do not affect the disposition of children to die of malignant neoplasm of the brain and malignant neoplasm of lymphatic and haemopoietic tissue.

Adolescent↗

Hyperspectral and multispectral bioluminescence optical tomography for small animal imaging.

For bioluminescence imaging studies in small animals, it is important to be able to accurately localize the three-dimensional (3D) distribution of the underlying bioluminescent source. The spectrum of light produced by the source that escapes the subject varies with the depth of the emission source because of the wavelength-dependence of the optical properties of tissue. Consequently, multispectral or hyperspectral data acquisition should help in the 3D localization of deep sources. In this paper, we describe a framework for fully 3D bioluminescence tomographic image acquisition and reconstruction that exploits spectral information. We describe regularized tomographic reconstruction techniques that use semi-infinite slab or FEM-based diffusion approximations of photon transport through turbid media. Singular value decomposition analysis was used for data dimensionality reduction and to illustrate the advantage of using hyperspectral rather than achromatic data. Simulation studies in an atlas-mouse geometry indicated that sub-millimeter resolution may be attainable given accurate knowledge of the optical properties of the animal. A fixed arrangement of mirrors and a single CCD camera were used for simultaneous acquisition of multispectral imaging data over most of the surface of the animal. Phantom studies conducted using this system demonstrated our ability to accurately localize deep point-like sources and show that a resolution of 1.5 to 2.2 mm for depths up to 6 mm can be achieved. We also include an in vivo study of a mouse with a brain tumour expressing firefly luciferase. Co-registration of the reconstructed 3D bioluminescent image with magnetic resonance images indicated good anatomical localization of the tumour.

Algorithms↗

Frequent loss of imprinting of PEG1/MEST in invasive breast cancer.

The human PEG1 gene is a newly identified imprinted gene on 7q32. Genetic aberrations of this chromosomal region are often detected in invasive breast carcinomas. In this study, we show monoallelic PEG1 expression in normal breast tissue, indicating the presence of a functional imprint, and more importantly, we demonstrate loss of imprinting (LOI) in all of seven informative invasive breast carcinomas. In contrast to this, in one case of atypical ductal hyperplasia (ADH) found in residual breast, imprinting was maintained. This raises the possibility that aberrant imprinting of PEG1 may be involved in the progression from hyperplasia to invasive breast cancer.

Alleles↗

A model for estimating the costs and burdens of breast cancer diagnosis and treatment in Canada.

As health care costs continue to rise in Canada, there is a need to evaluate the resources required for diagnosing and treating the major diseases having an impact on Canadian. In 1993, breast cancer was the most predominant female cancer in Canada, both in terms of incidence and mortality. It would be useful to identify the direct health care costs associated with this disease and to create an analytical framework within which diagnostic and therapeutic options can be assessed. This paper provides a description of the approach to be taken in developing a realistic conceptual model of the management of all stages of breast cancer, including diagnostic and treatment approaches, survival outcomes and costs. It includes an outline of our research objectives, a description of the kind of information required, a section on the methodology and sources to be used, and a brief explanation of the analytical framework into which it will be incorporated and used.

Adult↗

The clinical value of the determinations in the serum of zinc concentration in women with breast cancer.

The clinical usefulness of the determinations of the zinc serum concentration at different stages of the breast cancer diagnostic process was evaluated in the present work. On the basis of the analysis of 182 women surgically treated because of this neoplasm, a statistically significant dependence was shown between the frequency of occurrence of hypozincemia and the progression of the cancer, its histological form, and the microscopic state of the axillary lymph nodes. The clinical usefulness was also shown by the determinations of the zincemia in the post-operative monitoring of patients with breast cancer. The critical value was also determined for the microelement concentration below which a statistically significantly high risk of occurrence of distant metastases appears.

Adult↗

Sampling of grossly benign breast reexcisions: a multidisciplinary approach to assessing adequacy.

The widespread use of breast-conserving therapy in the treatment of early-stage breast cancer has resulted in increasing numbers of reexcision specimens requiring histologic assessment for residual disease and margin status. Because many reexcisions are performed for only microscopically positive or close margins, reexcision specimens often appear grossly negative and directed tissue sampling cannot be performed. The issue of adequate sampling in these specimens has not been addressed in the literature. A multidisciplinary approach to identifying the clinically important lesions in breast reexcisions and a cost-effective approach to tissue sampling are needed. We reviewed 97 consecutive cases of grossly negative breast reexcisions in which all tissue had been embedded. Forty-seven specimens contained residual invasive or in situ carcinoma and 50 were histologically negative. Detailed histologic findings were presented to a medical oncologist, a radiation oncologist, and a surgeon, who assessed the clinical impact of each diagnosis. Of the 47 positive specimens, 30 resulted in a major change in patient management (recommendation for additional surgery), 10 resulted in minor changes (alteration in radiation dose or adjuvant chemotherapy regimen), and 7 did not alter management. A total of 1867 blocks were submitted. If one block per centimeter of maximal tissue dimension had been submitted and the remainder of the specimen examined only if initial sections revealed invasive or in situ carcinoma, then 901 blocks would have been processed (52% reduction), but we would have missed an average of 3.7 cases resulting in a major change in therapy, and 3.3 cases resulting in a minor change. In contrast, two blocks per centimeter would have missed an average of less than one case each of diagnoses resulting in major and minor therapy changes (0.9 and 0.8 cases, respectively), and 315 (17%) fewer tissue blocks would have been processed. We recommend submitting two blocks per centimeter in grossly benign reexcisions, and examining the remainder of the tissue only if carcinoma is detected on initial sections.

Adult↗

A probability model for predicting BRCA1 and BRCA2 mutations in breast and breast-ovarian cancer families.

Germline mutations in BRCA1 and BRCA2 genes predispose to hereditary breast and ovarian cancer. Our aim was to find associations between the clinical characteristics and positive mutation status in 148 breast cancer families in order to predict the probability of finding a BRCA mutation in a family. Several factors were associated with mutations in univariate analysis, whereas in multivariate analysis (logistic regression with backward selection) only the age of the youngest breast cancer patient and the number of ovarian cancer cases in a family were independent predictors of BRCA mutations. A logistic model was devised to estimate the probability for a family of harbouring a mutation in either BRCA1 or BRCA2. Altogether, 63 out of 148 families (43%) and 28 out of 29 (97%) mutation carrier families obtained probabilities over 10%. The mean probability was 55% for mutation-positive families and 11% for mutation-negative families. The models by Couch et al (1997) and Shattuck-Eidens et al (1997) previously designed for BRCA1 were also tested for their applicability to distinguish carrier families with mutations in either gene. The probability model should be a useful tool in genetic counselling and focusing the mutation analyses, and thus increasing also the cost-effectiveness of the genetic screening.

Adult↗

Multi-class cancer classification via partial least squares with gene expression profiles.

MOTIVATION: Discrimination between two classes such as normal and cancer samples and between two types of cancers based on gene expression profiles is an important problem which has practical implications as well as the potential to further our understanding of gene expression of various cancer cells. Classification or discrimination of more than two groups or classes (multi-class) is also needed. The need for multi-class discrimination methodologies is apparent in many microarray experiments where various cancer types are considered simultaneously. RESULTS: Thus, in this paper we present the extension to the classification methodology proposed earlier Nguyen and Rocke (2002b; Bioinformatics, 18, 39-50) to classify cancer samples from multiple classes. The methodologies proposed in this paper are applied to four gene expression data sets with multiple classes: (a) a hereditary breast cancer data set with (1) BRCA1-mutation, (2) BRCA2-mutation and (3) sporadic breast cancer samples, (b) an acute leukemia data set with (1) acute myeloid leukemia (AML), (2) T-cell acute lymphoblastic leukemia (T-ALL) and (3) B-cell acute lymphoblastic leukemia (B-ALL) samples, (c) a lymphoma data set with (1) diffuse large B-cell lymphoma (DLBCL), (2) B-cell chronic lymphocytic leukemia (BCLL) and (3) follicular lymphoma (FL) samples, and (d) the NCI60 data set with cell lines derived from cancers of various sites of origin. In addition, we evaluated the classification algorithms and examined the variability of the error rates using simulations based on randomization of the real data sets. We note that there are other methods for addressing multi-class prediction recently and our approach is along the line of Nguyen and Rocke (2002b; Bioinformatics, 18, 39-50). CONTACT: dnguyen@stat.tamu.edu; dmrocke@ucdavis.edu

Algorithms↗

Detection of diagnostic clues in statistical histometry.

Examples are given of the detection of diagnostic clues in quantitative cytology and histopathology by statistical testing, such as may be applied in image analytical procedures. Schematic and other examples are presented of the visual images analyzed by each procedure, whose limits are also discussed. The situations analyzed include increased cellularity, differences in nuclear placement patterns, uniformity of displacement, variance in nuclear diameters and chaincode variance of nuclear placement. A specific model is presented for describing or generating a series of dependent observations representing nuclear placement, based on the Box-Jenkins (ARIMA) models for decomposing a spatial or temporal series into several components. This model describes the statistical observations that are random samples from the series. Finally, one graphic example is given in which visual inspection more readily ascertains an alteration than does statistical analysis of a modest-sized sample.

Analysis of Variance↗

Pitfalls and practice of Luria-Delbrück fluctuation analysis: a review.

Luria-Delbrück fluctuation analysis provides a method to estimate mutation rates in cell populations. Originally designed for bacterial populations, the method now is widely applied in somatic cell genetics and in cancer biology. However, there are fundamental genetic differences between bacteria and somatic cells, and this together with the inherent mathematical complexity of fluctuation analysis can lead to many pitfalls in its application. In addition there is considerable statistical error associated with the method. The use, misuse, and limitations of fluctuation analysis are reviewed here with the hope that such problems may be avoided.

Cells, Cultured↗

[Radiation-surgical treatment of cancer of the female breast].

Findings were reviewed of 1566 female patients with primary breast carcinoma treated with radical or total mastectomy followed by postoperative radiation therapy during the 22 year period 1960-82. The five-year overall survival for the axillary node-positive breast cancer group was 58.3 percent, as compared with 79.9 percent for the node-negative group. The survival rates were also analyzed in terms of age of the patients and number of the axillary positive nodes present. The ratios of observed deaths to expected deaths were turned from many times greater than unity into nearly the expected number, after ten year follow-up period. These findings showed that host factors are capable of destroying tumor cells both in node-negative and in node-positive patients. The significance of axillary negative nodes was emphasized. The rates of locoregional recurrences and distant metastases for node-negative patients were analyzed; these observations suggested that routine postoperative radiotherapy should be considered also in node-negative breast cancer patients.

Adolescent↗