Attitudes of 47 mothers of pediatric oncology patients toward genetic testing for cancer predisposition

PURPOSE: To assess attitudes toward testing for cancer susceptibility genes, we interviewed mothers of pediatric oncology patients about their cancer causation theories, interest in hypothetical predisposition testing for themselves and their healthy children, and anticipated impact of testing. PATIENTS AND METHODS: The subjects were 47 mothers of two or more living children, one of whom was 6 to 24 months postdiagnosis of cancer. Potential risks and benefits of hypothetical genetic predisposition testing for cancer susceptibility were described. A semistructured interview assessed the following: (1) recall of discussions with the pediatric oncologist about the possible role of heredity in causing the child's cancer; (2) mothers' personal theories of the etiology of their child's cancer; (3) family cancer history; (4) interest in genetic predisposition testing for themselves and unaffected (cancer-free) children; and (5) expected sequelae of testing. RESULTS: If genetic cancer predisposition tests were available, 51% of mothers would test themselves and 42% would test healthy children, even with no medical benefit. With established medical benefit, an additional 36% of mothers would seek testing for themselves and another 49% would test their healthy children. Interest in cancer predisposition testing among mothers extended far beyond those with significant family histories of cancer. Most mothers would consider minor children's wishes in the decision about testing and would tell children under age 18 their test results. CONCLUSION: As increasing numbers of cancer susceptibility genes are identified, parents of pediatric oncology patients may be receptive to opportunities to test themselves and their healthy children. Counseling will be important to aid in decisions about testing. Research is essential to evaluate the long-term impact of predisposition testing.     

Acquisition of selectional patterns in sublanguages

When implementing computational lexicons it is important to keep in mind the texts that a NLP system must deal with. Words relate to each other in many different, often odd ways this information is rarely found in dictionaries, and it is quite hard to deduce a priori. In this paper we present a technique for the acquisition of statistically significant selectional restrictions from corpora and discuss the results of an experimental application with reference to two specific sublaguages (legal and commercial). We show that there are important cooccurrence preferences among words which cannot be established a priori as they are determined for each choice of sublanguage. The method for detecting cooccurrences is based on the analysis of word associations augmented with syntactic markers and semantic tags. Word pairs are extracted by a morphosyntactic analyzer and clustered according to their semantic tags. A statistical measure is applied to the data to evaluate the sigificance of any relations detected. Selectional restrictions are acquired by a two-step process. First, statistically prevailing coarse grained conceptual patterns are used by a linguist to identify the relevant selectional restrictions in sublanguages. Second, semiautomatically acquired coarse selectional restrictions are used as the semantic bias of a system, ARIOSTO_LEX, for the automatic acquisition of a case-based semantic lexicon.     

Building knowledge through families of experiments

Experimentation in software engineering is necessary but difficult. One reason is that there are a large number of context variables and, so, creating a cohesive understanding of experimental results requires a mechanism for motivating studies and integrating results. It requires a community of researchers that can replicate studies, vary context variables, and build models that represent the common observations about the discipline. The paper discusses the experience of the authors, based upon a collection of experiments, in terms of a framework for organizing sets of related studies. With such a framework, experiments can be viewed as part of common families of studies, rather than being isolated events. Common families of studies can contribute to important and relevant hypotheses that may not be suggested by individual experiments. A framework also facilitates building knowledge in an incremental manner through the replication of experiments within families of studies. To support the framework, the paper discusses the experiences of the authors in carrying out empirical studies, with specific emphasis on persistent problems encountered in experimental design, threats to validity, criteria for evaluation, and execution of experiments in the domain of software engineering     

Rational Design,Synthesis, and DNA Binding Properties of Novel Sequence‐Selective Peptidyl Congeners of Ametantrone

Natural and synthetic compounds characterized by an anthraquinone nucleus represent an important class of anti‐neoplastic agents, the mechanism of action of which is related to intercalation into DNA. Ametantrone (AM) is a synthetic 9,10‐anthracenedione bearing two (hydroxyethylamino)ethylamino residues at positions 1 and 4; along with other anthraquinones and anthracyclines, it shares a polycyclic intercalating moiety and charged side chains that stabilize DNA binding. All these drugs elicit adverse side effects, which represent a challenge for antitumor chemotherapy. In the present work the structure of AM was augmented with appropriate groups that target well‐defined base pairs in the major groove. These should endow AM with DNA sequence selectivity. We describe the rationale for the synthesis and the evaluation of activity of a new series of compounds in which the planar anthraquinone is conjugated at positions 1 and 4 through the side chains of AM or other bioisosteric linkers to appropriate dipeptides. The designed novel AM derivatives were shown to selectively stabilize two oligonucleotide duplexes that both have a palindromic GC‐rich hexanucleotide core, but their stabilizing effects on a random DNA sequence was negligible. In the case of the most effective compound, the 1,4‐bis‐[Gly‐(L ‐Lys)] derivative of AM, the experimental results confirm the predictions of earlier theoretical computations. In contrast, AM had equal stabilizing effects on all three sequences and showed no preferential binding. This novel peptide derivative can be classified as a strong binder regarding the sequences that it selectively targets, possibly opening the exploitation of less cytotoxic conjugates of AM to the targeted treatment of oncological and viral diseases.     

Evaluating COTS component dependability in context

The software industry has increasingly expanded its adoption of COTS components for complex, mission-critical applications. Using COTS products can shorten development and deployment time because they let system developers focus on creating domain-specific services. Selecting the right COTS component, however, is no easy task. We present a practical process that developers can use to empirically evaluate component dependability in their context. Our approach uses the unified model of dependability, a requirements engineering approach specially devised to capture dependability in context. This model clearly specifies the measurable characteristics the component must have to be dependable in a specific context. The model then serves as a reference, providing guidance on effectively designing experiments to compare similar components and interpret collected data. The process can be applied to any specific context and COTS component. Here, we describe our comparison of the dependability of real-time Java virtual machines (RT JVM) in the spacecraft software context.