Abstract 1905: Defining a therapeutic classification of breast cancer by actionable targets

Breast cancer remains a frequent cause of female cancer death despite the great strides in elucidation of biological subtypes and their reported clinical and prognostic significance. We have defined a general cohort of breast cancers in terms of putative actionable targets, involving growth and proliferative factors, the cell cycle, and apoptotic pathways, both as single biomarkers across a general cohort and within intrinsic molecular subtypes.

We identified 293 patients treated with adjuvant chemotherapy. Additional hormonal therapy and trastuzumab was administered depending on hormonal and HER2 status respectively. We performed immunohistochemistry for ER, PR, HER2, MM1, CK5/6, p53, TOP2A, EGFR, IGF1R, PTEN, p-mTOR and e-cadherin. The cohort was classified into luminal (62%) and non-luminal (38%) tumors as well as luminal A (27%), luminal B HER2 negative (22%) and positive (12%), HER2 enriched (14%) and triple negative (25%). Patients with luminal tumors and co-overexpression of TOP2A or IGF1R loss displayed worse overall survival (p=0.0251 and p=0.0008 respectively). Non-luminal tumors had much greater heterogeneous expression profiles with no individual markers of prognostic significance. Non-luminal tumors were characterised by EGFR and TOP2A overexpression, IGF1R, PTEN and p-mTOR negativity and extreme p53 expression.

Our results indicate that only a minority of intrinsic subtype tumors purely express single novel actionable targets. This lack of pure biomarker expression is particular prevalent in the triple negative subgroup and may allude to the mechanism of targeted therapy inaction and myriad disappointing trial results. Utilising a combinatorial biomarker approach may enhance studies of targeted therapies providing additional information during design and patient selection while also helping decipher negative trial results.

Molecular classification of non-invasive breast lesions for personalised therapy and chemoprevention

Breast cancer screening has led to a dramatic increase in the detection of pre-invasive breast lesions. While mastectomy is almost guaranteed to treat the disease, more conservative approaches could be as effective if patients can be stratified based on risk of co-existing or recurrent invasive disease.Here we use a range of biomarkers to interrogate and classify purely non-invasive lesions (PNL) and those with co-existing invasive breast cancer (CEIN). Apart from Ductal Carcinoma In Situ (DCIS), relative homogeneity is observed. DCIS contained a greater spread of molecular subtypes. Interestingly, high expression of p-mTOR was observed in all PNL with lower expression in DCIS and invasive carcinoma while the opposite expression pattern was observed for TOP2A.Comparing PNL with CEIN, we have identified p53 and Ki67 as predictors of CEIN with a combined PPV and NPV of 90.48% and 43.3% respectively. Furthermore, HER2 expression showed the best concordance between DCIS and its invasive counterpart.We propose that these biomarkers can be used to improve the management of patients with pre-invasive breast lesions following further validation and clinical trials. p53 and Ki67 could be used to stratify patients into low and high-risk groups for co-existing disease. Knowledge of expression of more actionable targets such as HER2 or TOP2A can be used to design chemoprevention or neo-adjuvant strategies. Increased knowledge of the molecular profile of pre-invasive lesions can only serve to enhance our understanding of the disease and, in the era of personalised medicine, bring us closer to improving breast cancer care.

Classification of incomplete feature vectors by radial basis function networks

The paper describes the use of radial basis function neural networks with Gaussian basis functions to classify incomplete feature vectors. The method uses the fact that any marginal distribution of a Gaussian distribution can be determined from the mean vector and covariance matrix of the joint distribution.

Neural network classification of cerebral embolic signals

The presence of circulating cerebral emboli represents an increased risk of stroke. The detection of such emboli is possible with the use of a transcranial Doppler ultrasound (TCD) system.

Automatic classification of scientific records using the German Subject Heading Authority File (SWD)

The following paper deals with an automatic text classification method which does not require training documents. For this method the German Subject Heading Authority File (SWD), provided by the linked data service of the German National Library is used. Recently the SWD was enriched with notations of the Dewey Decimal Classification (DDC). In consequence it became possible to utilize the subject headings as textual representations for the notations of the DDC. Basically, we we derive the classification of a text from the classification of the words in the text given by the thesaurus. The method was tested by classifying 3826 OAI-Records from 7 different repositories. Mean reciprocal rank and recall were chosen as evaluation measure. Direct comparison to a machine learning method has shown that this method is definitely competitive. Thus we can conclude that the enriched version of the SWD provides high quality information with a broad coverage for classification of German scientific articles.

Statistical classification of road pavements using near field vehicle rolling noise measurements

Low noise surfaces have been increasingly considered as a viable and cost-effective alternative to acoustical barriers. However, road planners and administrators frequently lack information on the correlation between the type of road surface and the resulting noise emission profile. To address this problem, a method to identify and classify different types of road pavements was developed, whereby near field road noise is analyzed using statistical learning methods. The vehicle rolling sound signal near the tires and close to the road surface was acquired by two microphones in a special arrangement which implements the Close-Proximity method. A set of features, characterizing the properties of the road pavement, was extracted from the corresponding sound profiles. A feature selection method was used to automatically select those that are most relevant in predicting the type of pavement, while reducing the computational cost. A set of different types of road pavement segments were tested and the performance of the classifier was evaluated. Results of pavement classification performed during a road journey are presented on a map, together with geographical data. This procedure leads to a considerable improvement in the quality of road pavement noise data, thereby increasing the accuracy of road traffic noise prediction models.

Data mining techniques to support the classification of MV electricity customers

This paper describes a methodology that was developed for the classification of Medium Voltage (MV) electricity customers. Starting from a sample of data bases, resulting from a monitoring campaign, Data Mining (DM) techniques are used in order to discover a set of a MV consumer typical load profile and, therefore, to extract knowledge regarding to the electric energy consumption patterns. In first stage, it was applied several hierarchical clustering algorithms and compared the clustering performance among them using adequacy measures. In second stage, a classification model was developed in order to allow classifying new consumers in one of the obtained clusters that had resulted from the previously process. Finally, the interpretation of the discovered knowledge are presented and discussed.

A Classification of Feminist Theories

In this paper I criticize Alison Jaggar’s descriptions of feminist political theories. I propose an alternative classification of feminist theories that I think more accurately reflects the multiplication of feminist theories and philosophies. There are two main categories, “street theory” and academic theories, each with two sub-divisions, political spectrum and “differences” under street theory, and directly and indirectly political analyses under academic theories. My view explains why there are no radical feminists outside of North America and why there are so few socialist feminists inside North America. I argue, controversially, that radical feminism is a radical version of liberalism. I argue that “difference” feminist theories – theory by and about feminists of colour, queer feminists, feminists with disabilities and so on – belong in a separate sub-category of street theory, because they’ve had profound effects on feminist activism not tracked by traditional left-to-right classifications. Finally, I argue that, while academic feminist theories such as feminist existentialism or feminist sociological theory are generally unconnected to movement activism, they provide important feminist insights that may become importanby showing the advantages of my classification over Jaggar’s views.

Classification of Handwritten Characters: Definition, Identification and Utilisation of Regional Characteristics for Lower Case English Characters

A new procedure for the classification of lower case English language characters is presented in this work . The character image is binarised and the binary image is further grouped into sixteen smaller areas ,called Cells . Each cell is assigned a name depending upon the contour present in the cell and occupancy of the image contour in the cell. A data reduction procedure called Filtering is adopted to eliminate undesirable redundant information for reducing complexity during further processing steps . The filtered data is fed into a primitive extractor where extraction of primitives is done . Syntactic methods are employed for the classification of the character . A decision tree is used for the interaction of the various components in the scheme . 1ike the primitive extraction and character recognition. A character is recognized by the primitive by primitive construction of its description . Openended inventories are used for including variants of the characters and also adding new members to the general class . Computer implementation of the proposal is discussed at the end using handwritten character samples . Results are analyzed and suggestions for future studies are made. The advantages of the proposal are discussed in detail .