Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

Demonstration of the Blood-Stage Plasmodium falciparum Controlled Human Malaria Infection Model to Assess Efficacy of the P. falciparum Apical Membrane Antigen 1 Vaccine, FMP2.1/AS01

We study whether the relationship between the state unemployment rate at the time of conception and infant health, infant mortality and maternal characteristics in the United States has changed over the years 1980-2004. We use microdata on births and deaths for years 1980-2004 and find that the relationship between the state unemployment rate at the time of conception and infant mortality and birthweight changes over time and is stronger for blacks than whites. For years 1980-1989 increases in the state unemployment rate are associated with a decline in infant mortality among blacks, an effect driven by mortality from gestational development and birth weight, and complications of placenta while in utero. In contrast, state economic conditions are unrelated to black infant mortality in years 1990-2004 and white infant mortality in any period, although effects vary by cause of death. We explore potential mechanisms for our findings and, including mothers younger than 18 in the analysis, uncover evidence of age-related maternal selection in response to the business cycle. In particular, in years 1980-1989 an increase in the unemployment rate at the time of conception is associated with fewer babies born to young mothers. The magnitude and direction of the relationship between business cycles and infant mortality differs by race and period. Age-related selection into motherhood in response to the business cycle is a possible explanation for this changing relationship

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety ‘Mode of Action’ framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/ mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety ‘Mode of Action’ framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

Day 2-end of Chute presentation.mp3

Generating recommendations in OPACS: initial results and open areas for exploration : In the context of a research and prototyping project, the California Digital Library is using catalog content indexed in XTF, along with over 9 million historical circulation transaction records and other external data, to generate recommendations for an academic audience. Early results are promising. This talk will focus on methods, challenges, and plans for further development. -- Library Text Mining : Using the TeraGrid1 and the SRB DataGrid2, we have sufficient computational and storage facilities to run normally prohibitively expensive processing tasks. By integrating text and data mining tools3[4] within the Cheshire35 information architecture, we can parse the natural language present in 20 million MARC records (the University of California's MELVYL collection) and extract information to provide to search/retrieve applications. In this talk, we'll discuss the results of applying new techniques to "old" data. -- Anatomy of aDORe : The aDORe Archive is a write-once/read-many storage approach for Digital Objects and their constituent datastreams. First, XML-based representations of multiple Digital Objects are concatenated into a single, valid XML file named an XMLtape. Second, ARC files, as introduced by the Internet Archive, are used to contain the constituent datastreams of the Digital Objects. The software was developed by the LANL Digital Library Research & Prototyping Team and is available under GNU LGPL license

Day 2am-2.mp3

Generating recommendations in OPACS: initial results and open areas for exploration : In the context of a research and prototyping project, the California Digital Library is using catalog content indexed in XTF, along with over 9 million historical circulation transaction records and other external data, to generate recommendations for an academic audience. Early results are promising. This talk will focus on methods, challenges, and plans for further development. -- Library Text Mining : Using the TeraGrid1 and the SRB DataGrid2, we have sufficient computational and storage facilities to run normally prohibitively expensive processing tasks. By integrating text and data mining tools3[4] within the Cheshire35 information architecture, we can parse the natural language present in 20 million MARC records (the University of California's MELVYL collection) and extract information to provide to search/retrieve applications. In this talk, we'll discuss the results of applying new techniques to "old" data. -- Anatomy of aDORe : The aDORe Archive is a write-once/read-many storage approach for Digital Objects and their constituent datastreams. First, XML-based representations of multiple Digital Objects are concatenated into a single, valid XML file named an XMLtape. Second, ARC files, as introduced by the Internet Archive, are used to contain the constituent datastreams of the Digital Objects. The software was developed by the LANL Digital Library Research & Prototyping Team and is available under GNU LGPL license

code4lib Conference 2006, February 16, 2006 : morning session

Presentation given on the second day of the code4lib Conference held Feb. 15-17, 2006, at LaSells Stewart Center, Oregon State University, Corvallis, Oregon.Generating recommendations in OPACS: initial results and open areas for exploration : In the context of a research and prototyping project, the California Digital Library is using catalog content indexed in XTF, along with over 9 million historical circulation transaction records and other external data, to generate recommendations for an academic audience. Early results are promising. This talk will focus on methods, challenges, and plans for further development. -- Library Text Mining : Using the TeraGrid1 and the SRB DataGrid2, we have sufficient computational and storage facilities to run normally prohibitively expensive processing tasks. By integrating text and data mining tools3[4] within the Cheshire35 information architecture, we can parse the natural language present in 20 million MARC records (the University of California's MELVYL collection) and extract information to provide to search/retrieve applications. In this talk, we'll discuss the results of applying new techniques to "old" data. -- Anatomy of aDORe : The aDORe Archive is a write-once/read-many storage approach for Digital Objects and their constituent datastreams. First, XML-based representations of multiple Digital Objects are concatenated into a single, valid XML file named an XMLtape. Second, ARC files, as introduced by the Internet Archive, are used to contain the constituent datastreams of the Digital Objects. The software was developed by the LANL Digital Library Research & Prototyping Team and is available under GNU LGPL license