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

On a Penrose Inequality with Charge

We construct a time-symmetric asymptotically flat initial data set to the Einstein-Maxwell Equations which satisfies the inequality: m - 1/2(R + Q^2/R) < 0, where m is the total mass, R=sqrt(A/4) is the area radius of the outermost horizon and Q is the total charge. This yields a counter-example to a natural extension of the Penrose Inequality to charged black holes.Comment: Minor revision: some typos; author's address updated; bibliographical reference added; journal information: to appear in Comm. Math. Phy

Validation of a Predictive Model for Survival in Patients With Advanced Cancer: Secondary Analysis of RTOG 9714.

BackgroundThe objective of this study was to validate a simple predictive model for survival of patients with advanced cancer.MethodsPrevious studies with training and validation datasets developed a model predicting survival of patients referred for palliative radiotherapy using three readily available factors: primary cancer site, site of metastases and Karnofsky performance score (KPS). This predictive model was used in the current study, where each factor was assigned a value proportional to its prognostic weight and the sum of the weighted scores for each patient was survival prediction score (SPS). Patients were also classified according to their number of risk factors (NRF). Three risk groups were established. The Radiation Therapy and Oncology Group (RTOG) 9714 data was used to provide an additional external validation set comprised of patients treated among multiple institutions with appropriate statistical tests.ResultsThe RTOG external validation set comprised of 908 patients treated at 66 different radiation facilities from 1998 to 2002. The SPS method classified all patients into the low-risk group. Based on the NRF, two distinct risk groups with significantly different survival estimates were identified. The ability to predict survival was similar to that of the training and previous validation datasets for both the SPS and NRF methods.ConclusionsThe three variable NRF model is preferred because of its relative simplicity

Convergence and generalization of a recursion equation for primes

The main result is a generalization of Keller's recursion equation for finding a prime number given the previous primes. We also examine the convergence of the limit in Keller's equation and the convergence of the limit in the general equation. The latter is dependent on the choice of L-function

Heated element fluid flow sensor Patent

Heated element sensor for fluid flow detection in thermal conductive conduit with adaptive means to determine flow rate and directio

Engaged Leadership: New Concept or Evolutionary in Nature?

Mr. Woods provides a critique and a book review of Clint Swindall‘s Engaged Leadership. His accolades relate primarily to Swindell‘s communication of connecting the dynamics of a work environment and the applications of engaged leadership in fable format. He decries, however, the author‘s missed opportunities to further associate engaged leadership to an established theory of management and to use polling data which attempts to ascertain any cost savings associated with engaged leadership