“Unmixing” Tissue Gene Expression Signatures from Tumor Biopsies

Emergent molecular measurement methods, such as DNA microarray, qRTPCR, and many others, offer tremendous promise for the personalized treatment of cancer. These technologies measure the amount of specific proteins, RNA, DNA or other molecular targets from tumor specimens with the goal of “fingerprinting” individual cancers. Tumor specimens are heterogeneous; an individual specimen typically contains unknown amounts of multiple tissues types. Thus, the measured molecular concentrations result from an unknown mixture of tissue types, and must be normalized to account for the composition of the mixture. For example, a breast tumor biopsy may contain normal, dysplastic and cancerous epithelial cells, as well as stromal components (fatty and connective tissue) and blood and lymphatic vessels. Our diagnostic interest focuses solely on the dysplastic and cancerous epithelial cells. The remaining tissue components serve to “contaminate” the signal of interest. The proportion of each of the tissue components changes as a function of patient characteristics (e.g., age), and varies spatially across the tumor region. Because each of the tissue components produces a different molecular signature, and the amount of each tissue type is specimen dependent, we must estimate the tissue composition of the specimen, and adjust the molecular signal for this composition. Using the idea of a chemical mass balance, we consider the total measured concentrations to be a weighted sum of the individual tissue signatures, where weights are determined by the relative amounts of the different tissue types. We develop a compositional source apportionment model to estimate the relative amounts of tissue components in a tumor specimen. We then use these estimates to infer the tissuespecific concentrations of key molecular targets for sub-typing individual tumors. We anticipate these specific measurements will greatly improve our ability to discriminate between different classes of tumors, and allow more precise matching of each patient to the appropriate treatment

Adaptive intelligent agent approach to guide the web navigation on the PLAN-G distance learning platform

Hypermedia systems based on the Web for open distance education are becoming increasingly popular as tools for user-driven access learning information. Adaptive hypermedia is a new direction in research within the area of user-adaptive systems, to increase its functionality by making it personalized [Eklu 961. This paper sketches a general agents architecture to include navigational adaptability and user-friendly processes which would guide and accompany the student during hislher learning on the PLAN-G hypermedia system (New Generation Telematics Platform to Support Open and Distance Learning), with the aid of computer networks and specifically WWW technology [Marz 98-1] [Marz 98-2]. The PLAN-G actual prototype is successfully used with some informatics courses (the current version has no agents yet). The propased multi-agent system, contains two different types of adaptive autonomous software agents: Personal Digital Agents {Interface), to interacl directly with the student when necessary; and Information Agents (Intermediaries), to filtrate and discover information to learn and to adapt navigation space to a specific student

A teaching/learning support tool for introductory programming courses

In This work we present a Web-based tool developed with the aim of reinforcing teaching and learning of introductory programming courses. This tool provides support for teaching and learning. From the teacher's perspective the system introduces important gains with respect to the classical teaching methodology. It reinforces lecture and laboratory sessions, makes it possible to give personalized attention to the student, assesses the degree of participation of the students and most importantly, performs a continuous assessment of the student's progress. From the student's perspective it provides a learning framework, consisting in a help environment and a correction environment, which facilitates their personal work. With this tool students are more motivated to do programming

Breast cancer incidence and overdiagnosis in Catalonia (Spain)

Early detection of breast cancer (BC) with mammography may cause overdiagnosis and overtreatment, detecting tumors which would remain undiagnosed during a lifetime. The aims of this study were: first, to model invasive BC incidence trends in Catalonia (Spain) taking into account reproductive and screening data; and second, to quantify the extent of BC overdiagnosis. We modeled the incidence of invasive BC using a Poisson regression model. Explanatory variables were: age at diagnosis and cohort characteristics (completed fertility rate, percentage of women that use mammography at age 50, and year of birth). This model also was used to estimate the background incidence in the absence of screening. We used a probabilistic model to estimate the expected BC incidence if women in the population used mammography as reported in health surveys. The difference between the observed and expected cumulative incidences provided an estimate of overdiagnosis.Incidence of invasive BC increased, especially in cohorts born from 1940 to 1955. The biggest increase was observed in these cohorts between the ages of 50 to 65 years, where the final BC incidence rates more than doubled the initial ones. Dissemination of mammography was significantly associated with BC incidence and overdiagnosis. Our estimates of overdiagnosis ranged from 0.4% to 46.6%, for women born around 1935 and 1950, respectively.Our results support the existence of overdiagnosis in Catalonia attributed to mammography usage, and the limited malignant potential of some tumors may play an important role. Women should be better informed about this risk. Research should be oriented towards personalized screening and risk assessment tools