With the release of the landmark report Toxicity Testing in the 21st Century: A Vision and a Strategy, the U.S. National Academy of Sciences, in 2007, precipitated a major change in the way toxicity testing is conducted. It envisions increased efficiency in toxicity testing and decreased animal usage by transitioning from current expensive and lengthy in vivo testing with qualitative endpoints to in vitro toxicity pathway assays on human cells or cell lines using robotic high-throughput screening with mechanistic quantitative parameters. Risk assessment in the exposed human population would focus on avoiding significant perturbations in these toxicity pathways. Computational systems biology models would be implemented to determine the dose-response models of perturbations of pathway function. Extrapolation of in vitro results to in vivo human blood and tissue concentrations would be based on pharmacokinetic models for the given exposure condition. This practice would enhance human relevance of test results, and would cover several test agents, compared to traditional toxicological testing strategies. As all the tools that are necessary to implement the vision are currently available or in an advanced stage of development, the key prerequisites to achieving this paradigm shift are a commitment to change in the scientific community, which could be facilitated by a broad discussion of the vision, and obtaining necessary resources to enhance current knowledge of pathway perturbations and pathway assays in humans and to implement computational systems biology models. Implementation of these strategies would result in a new toxicity testing paradigm firmly based on human biology.

The war against cancer is far from over. Observed changes in mortality due to cancer primarily reflect changing incidence or early detection. The effect of new treatments for cancer on mortality has been largely disappointing. The most promising approach to the control of cancer is a national commitment to prevention, with a concomitant rebalancing of the focus and funding of research.

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Stereospecific effects are observed in many of the reactions of complex ions which contain optically active coordinating agents. Some examples of such stereospecificity are described, and an explanation of them is given which depends on an analysis of the stereochemistry of individual chelate rings and of the relationship between the rings in bis-and tris-chelate complexes. For example, it is shown that the dextro-and Zero-forms of [Co en3] +3 can each exist in four conformational forms which differ in stability and which are in rapid equilibrium. One of these forms, designated herein as the "lei" form, is consideiably more stable than the other three. The stereochemical requirements of the stable lei form are such that when a racemic 1,2-diamine is substituted for ethylenediamine all three ligands in the complex possess the same configuration. Hence, from a racemic 1,2-diamine, two isomers predominate at equilibrium, and its enantiomer [Codamine )3] +3. The approach which has been developed makes possible predictions of relative stabilities and reactivities of isomers and allows the assignment of absolute configuration to chelate compounds.

BACKGROUND: Inclusion of diverse groups of participants in cancer clinical trials is an important methodological and clinical issue. The quality of the science and generalizability of results depends on the inclusion of study participants who represent all populations among whom these treatment and prevention approaches will be used. METHODS: We conducted a systematic review using OVID as the primary source of reports included. Based on 304 peer-reviewed publications, diversity in the inclusion and reporting of study participants during a decade of cancer treatment and prevention trials (2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009)(2010) is summarized. Recommendations are made for improvements in the science and reporting of cancer clinical trials. RESULTS: Of the 277 treatment trials and 27 prevention trials included in this report, more than 80% of participants were white and 59.8% were male. In the recent decade, race and sex are rarely used as selection criteria unless the trial is focused on a sex-specific cancer. 1 Their results were not encouraging. We report an update of that study, focused on identifying changes in enrollment in cancer treatment and prevention clinical trials a decade later (2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009)(2010).It is understood that cancer treatment and preventive efforts are not generalizable to the entire treatable population. Historically, however, the majority of studies assessing the effectiveness of cancer treatment and prevention has been conducted using white men.1 An improved understanding of the differences between subgroups (race/ethnicity and sex) is critical to improving the risk/benefit profile for a wide range of chemotherapeutics and prevention efforts.Though much effort had been devoted to planning and implementation of programs aimed at reducing health disparities, the 2002 paper reported that minorities were still unlikely to be enrolled in clinical trials. There were 105 treatment trials that reported including both men and women, representing 42,355 participants; 38.6% of the participants were women. Results were fairly similar (34.7% of the participants were women) for the prevention studies. Age distribution and sex were reported in more than 90% of the trials (both treatment and prevention), yet race or ethnicity were reported in only 35.1% of the included treatment trials and 53.6% of the prevention trials. Within the 57 treatment trials (with 45,815 participants) which reported race or ethnicity, 10.5% of participants were reported as African American, and fewer than 1% were reported as Hispanic, Asian, or Native American. There was even less racial and ethnic diversity within the prevention trials: only 5.5% of participants were African American, 1.7% were Hispanic, and fewer than 1% were Asian or Native American.