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

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

Non-Parametric Framework for Detecting Spectral Anomalies in Hyperspectral Images

Over the past few years, hyperspectral data exploitation aimed at detecting spectral anomalies within remotely sensed images has been of growing interest in many applications. In this letter, we are interested in an anomaly detection (AD) scheme for hyperspectral images in which spectral anomalies are defined with respect to a statistical model of the background probability density function (PDF). Among the multitude of PDF estimators discussed in statistics literature, Parzen windowing (PW) has always attracted much attention. However, its ability to estimate the PDF of global background in order to detect anomalies in hyperspectral images has not been investigated yet. Here, we propose the use of PW to provide reliable background PDF estimation. As is widely recognized, PW performance is primarily affected by the choice of the bandwidth matrix, which controls the degree of smoothing for the resulting PDF approximation. In this letter, the bandwidth selection problem is approached, resorting to an unsupervised method based on a Bayesian approach. Once the background PDF is approximated through PW, it is employed to detect anomalous objects within the scene by using the likelihood ratio test

Background Density Nonparametric Estimation With Data-Adaptive Bandwidths for the Detection of Anomalies in Multi-Hyperspectral Imagery

This letter presents a scheme for detecting global anomalies, in which a likelihood ratio test based decision rule is applied in conjunction with an automated data-driven estimation of the background probability density function (PDF). The latter is reliably estimated with a nonparametric variable-band width kernel density estimator (VKDE), without making any distributional assumption. With respect to conventional fixed bandwidth KDE (FKDE), which lacks adaptivity due to the use of a bandwidth that is fixed across the entire feature space, VKDE lets the bandwidths adaptively vary pixel by pixel, tailoring the amount of smoothing to the local data density. Two multispectral images are employed to explore the potential of VKDE background PDF estimation for detecting anomalies in a scene with respect to conventional nonadaptive FKDE

A Locally Adaptive Background Density Estimator: An Evolution for RX-Based Anomaly Detectors

We propose a local anomaly detection strategy for multi-hyperspectral images in which the background probability density function is estimated with a kernel density estimator and locally adaptive information extracted from the image is injected into the bandwidth selection process. Results for multispectral images of different scenarios show the benefits of the proposed strategy regarding its effectiveness both at detecting anomalies and at avoiding the crucial issue of properly selecting the kernel-width parameter

Models and Methods for Automated Background Density Estimation in Hyperspectral Anomaly Detection

Anomaly detection (AD) in remotely sensed hyperspectral images has been proven to be valuable in many applications. In this paper, we propose a scheme for detecting global anomalies in which a likelihood ratio test-based decision rule is applied in conjunction with automated data-driven estimation of the background probability density function (PDF). Specifically, the use of both semiparametric (finite mixtures) and nonparametric (Parzen windows) models is investigated for background PDF estimation. Although such approaches are well known in multivariate data analysis, they have been very seldom applied to estimate the hyperspectral image background PDF, mostly due to the difficulty of reliably learning the model parameters without operator intervention. In this paper, semi and nonparametric estimators have been successfully employed to estimate the image background PDF with the aim of detecting global anomalies in a scene benefiting from the application of ad hoc Bayesian learning strategies. Two real hyperspectral images have been used to experimentally evaluate the ability of the proposed AD scheme resulting from the application of different global background PDF models and learning methods

Quadriceps tendon tear rupture in healthy patients treated with patellar drilling holes: clinical and ultrasonographic analysis after 36 months of follow-up

Background: quadriceps tendon subcutaneous rupture is an uncommon injury affecting predominantly middle-aged men as a result of direct or indirect trauma; aim of this work is to evaluate clinical outcome and tendon morphology in patients treated surgically with transpatellar drilling suture. Methods: 20 patients (20 male) with an average age of 54 (42-59) were evaluated with a mean follow-up of 36 months. Measurements of range of motion (ROM) and of tight circumference were collected. Lysholm and Rougraff Score were also performed. All the patients underwent a US evaluation the morphologic changes of the repaired tendon. Results: mean active ROM was 1°-117°; average difference in the circumference of the quadriceps was 2.6% 10 C and 3.3% 15 C. The mean Lysholm Score calculated was 88/100; the mean Rougraff Score 17/25. At ultrasonographic evaluation all tendons were continuous; heterotopic ossification was present in 18 quadriceps tendons. Thickness was augmented in 18 quadriceps tendons and in 5 patellar tendons. Vascularization was always conserved. Lateral subluxation of patella was reported in 1 case. Conclusions: patellar drilling holes repair is a nondemanding procedure, inexpensive and technically uncomplicated. US evaluation confirms tendon healing; tendon remodeling does not affect patient’s clinical outcome and quality of life