Sex-change chemicals and their influence on the brain.

The potential for man-made chemicals to mimic or antagonise natural hormones is a controversial issue, but one for which increasing amounts of evidence are being gathered worldwide. The controversy surrounds not so much the matter of whether these chemicals can mimic hormones in vitro--this phenomenon has been widely accepted in the scientific world - but more whether, as a result, they can disrupt reproduction in a wildlife situation. It has, nevertheless, been acknowledged that many wildlife populations are exhibiting reproductive and/or developmental abnormalities such as intersex gonads in wild roach populations in the U.K. and various reproductive disorders in alligators in Lake Apopka, Florida. However, the causative agents for many of these effects are difficult to specify, due to the extensive mixtures of chemicals--each of which may act via different pathways--to which wild populations are exposed, together with the wide variability observed even in natural (uncontaminated) habitats. As a result, any information detailing fundamental mechanism of action of the so-called endocrine disrupting chemicals (EDCs) is of use in determining whether or not these chemicals, as they are present in the environment, may in fact be capable of causing some of the effects observed in wildlife over recent years

Issues arising when interpreting results from an in vitro assay for estrogenic activity

Concern about possible adverse effects caused by the inadvertent exposure of humans and wildlife to endocrine-active chemicals, has led some countries to develop an in vivo–in vitro screening program for endocrine effects. In this paper, a previously described estrogen-inducible recombinant yeast strain (Saccharomyces cerevisiae) is used to investigate a number of issues that could potentially lead to the mislabeling of chemicals as endocrine disruptors. The chemicals studied were: 17-estradiol, dihydrotestosterone, testosterone, estradiol-3-sulfate, 4-nonylphenol, 4-tert-octylphenol, 4-tert-butylphenol, bisphenol-A, methoxychlor, 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane, butyl benzyl phthalate, 4-hydroxytamoxifen, and ICI 182,780. Alterations in assay methodology (for example, incubation time, initial yeast cell number, and the use of different solvents) did not affect the potency of bisphenol-A and 4-nonylphenol relative to 17-estradiol, but did alter the apparent potency of butyl benzyl phthalate. Other issues (including the metabolic activation of methoxychlor, the chemical purity of a steroid metabolite and unusual chemical artifacts observed with alkylphenolic chemicals) which affect data interpretation are described. Many of the issues raised will also affect other in vitro assays for endocrine activity, and some will be relevant to the interpretation of data from in vivo assays. These examples illustrate that considerable care and thought must be applied when interpreting results derived from any single assay. Only by using a suite of assays will we minimize the chances of wrongly labeling chemicals as endocrine disruptors

Applying moral foundations theory to understanding public views of sexual offending

Much research has examined the views held by citizens about sexual offenders and related policy responses. Although studies have extensively examined demographic correlates of such views, little attention has been paid to psychological mechanisms that underpin them. Gaining a deeper understanding of such mechanisms may ultimately prove useful for informing communication strategies around the problem of sexual violence. We propose the application of moral foundations theory (MFT) as a means of exploring the roots of the current punitive consensus around sexual crime policy at the macro level, as well as individual variability in attitudes about sexual violence. Following an overview of the sexual offender policy landscape, and a description of MFT principles, we outline how this framework can help to explain both convergence and divergence in responses to sexual offending among members of the public. We also provide a series of testable hypotheses to stimulate further research in this area

Benzotriazole is antiestrogenic in vitro but not in vivo

Copyright © 2007 SETAC. This is the accepted version of the following article: Harris et al (2007), "Benzotriazole is antiestrogenic in vitro but not in vivo", Environmental Toxicology and Chemistry, 26(11), 2367–2372, which has been published in final form at the link below.Benzotriazole (BT) is an anticorrosive agent well known for its use in aircraft deicing and antifreeze fluids but also used in dishwasher detergents. It is highly persistent in the environment; therefore, BT is frequently found in runoff emanating from large airports as well as in the surrounding groundwater. In addition, BT has recently been found to be ubiquitous in Swiss wastewater treatment plant effluents and their receiving waters; however, very little chronic toxicity data is available on which to base a sound ecological risk assessment of this chemical. In vitro assays conducted using a recombinant yeast (anti-) estrogen assay indicated that BT possessed clear antiestrogenic properties. This chemical was approximately 100-fold less potent than Tamoxifen, which was used as a positive control. A subsequent in vivo study, however, involving analysis of vitellogenin induction and somatic indices in adult fathead minnows (Pimephales promelas) exposed to BT at concentrations of 10, 100, and 1,000 μg/L for two weeks showed no evidence of antiestrogenic activity by this compound. The possibility exists that higher concentrations of BT may yet induce the type of activity observed in vitro, although the concentrations used here already far exceed those reported in surface-water samples. Furthermore, adverse effects may be observed in fish or other organisms exposed to BT for a longer period than employed here, although such studies are costly and unlikely to be included in standard risk assessment procedures. A rigorous investigation of the chronic toxicity of BT is imperative

The influence of a surfactant, linear alkylbenzene sulfonate, on the estrogenic response to a mixture of (xeno)estrogens in vitro and in vivo

This is the post-print version of the final paper published in Aquatic Toxicology. The published article is available from the link below. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. Copyright © 2008 Elsevier B.V. All rights reserved.The effect of the presence of a surfactant on the activity of a mixture of environmental estrogens was assessed. In their natural habitat, fish are subject not only to exposure to mixtures of estrogenic compounds, as has been addressed in previous publications, but also to other confounding factors (chemical, physical and biological), which may, in theory, affect their responses to such compounds. To assess the potential for such interference, the commonly occurring surfactant, linear alkylbenzene sulfonate (LAS), was applied to the yeast estrogen screen at various concentrations, independently and together with a mixture of estrogens at constant concentrations. LAS enhanced the estrogenic activity of the mixture, an effect which became less pronounced over the course of time. This information was used to design an in vivo study to assess induction of vitellogenin in fathead minnows exposed to the same mixture of estrogens plus LAS. A similar trend was observed, that is, the response was enhanced, but the effect became less pronounced as the study progressed. However, the enhanced response in vivo occurred only at the highest concentration of LAS tested (362 μg/L), and was transient because it was no longer apparent by the end of the study. Although LAS is a significant contaminant in terms of both concentration and frequency of detection in the aquatic environment, these data do not suggest that it will have a significant impact on the response of fish to environmental estrogens

Evidence of estrogenic mixture effects on the reproductive performance of fish

The official published version can be obtained from the link below - Copyright @ 2007 American Chemical SocietyRecent research into the effects of mixtures of estrogenic chemicals has revealed the capacity for similarly acting chemicals to act in combination, according to the principles of concentration addition. This means that, collectively, they may pose a significant environmental risk, even when each component is present at a low and individually ineffective concentration. The aim of this study was to investigate the ecological significance of mixture effects at low-effect concentrations by assessing the combined effect of estrogenic chemicals on the reproductive performance of fish. Pairs of fathead minnows were exposed to five estrogenic chemicals. Endpoints analyzed included fecundity, the expression of male secondary sexual characteristics, somatic indices, and vitellogenin induction. In the first phase of the study, a concentration-response analysis was performed to investigate the relative sensitivity of these endpoints. In the second phase, mixture effects at low-effect concentrations were explored by exposing fish to each of the mixture components, individually and in combination. Data from these experiments provide evidence of mixture effects on fitness and fecundity, demonstrating the capacity for chemicals to act together to affect reproductive performance, even when each component is present belowthe threshold of detectable effects. This has important implications for hazard assessment and contributes to our understanding of mixture effects at increasing levels of biological complexity.This work was funded by the European Commission, under contract EVK1-2001-00091

Data-Driven Stability Assessment of Multilayer Long Short-Term Memory Networks

Recurrent Neural Networks (RNNs) are increasingly being used for model identification, forecasting and control. When identifying physical models with unknown mathematical knowledge of the system, Nonlinear AutoRegressive models with eXogenous inputs (NARX) or Nonlinear AutoRegressive Moving-Average models with eXogenous inputs (NARMAX) methods are typically used. In the context of data-driven control, machine learning algorithms are proven to have comparable performances to advanced control techniques, but lack the properties of the traditional stability theory. This paper illustrates a method to prove a posteriori the stability of a generic neural network, showing its application to the state-of-the-art RNN architecture. The presented method relies on identifying the poles associated with the network designed starting from the input/output data. Providing a framework to guarantee the stability of any neural network architecture combined with the generalisability properties and applicability to different fields can significantly broaden their use in dynamic systems modelling and control

The consequences of feminization in breeding groups of wild fish

EHP is a publication of the U.S. government. Publication of EHP lies in the public domain and is therefore without copyright. Research articles from EHP may be used freely; however, articles from the News section of EHP may contain photographs or figures copyrighted by other commercial organizations and individuals that may not be used without obtaining prior approval from both the EHP editors and the holder of the copyright. Use of any materials published in EHP should be acknowledged (for example, "Reproduced with permission from Environmental Health Perspectives") and a reference provided for the article from which the material was reproduced.BACKGROUND: The feminization of nature by endocrine-disrupting chemicals (EDCs) is a key environmental issue affecting both terrestrial and aquatic wildlife. A crucial and as yet unanswered question is whether EDCs have adverse impacts on the sustainability of wildlife populations. There is widespread concern that intersex fish are reproductively compromised, with potential population-level consequences. However, to date, only in vitro sperm quality data are available in support of this hypothesis. OBJECTIVE: The aim of this study was to examine whether wild endocrine-disrupted fish can compete successfully in a realistic breeding scenario. METHODS: In two competitive breeding experiments using wild roach (Rutilus rutilus), we used DNA microsatellites to assign parentage and thus determine reproductive success of the adults. RESULTS: In both studies, the majority of intersex fish were able to breed, albeit with varying degrees of success. In the first study, where most intersex fish were only mildly feminized, body length was the only factor correlated with reproductive success. In the second study, which included a higher number of more severely intersex fish, reproductive performance was negatively correlated with severity of intersex. The intersex condition reduced reproductive performance by up to 76% for the most feminized individuals in this study, demonstrating a significant adverse effect of intersex on reproductive performance. CONCLUSION: Feminization of male fish is likely to be an important determinant of reproductive performance in rivers where there is a high prevalence of moderately to severely feminized males.Funding for this work was derived through the Endocrine Disruption in Catchments project, which was supported by the U.K. Department for Environment Food and Rural Affairs and the U.K. Environment Agency

Autonomous Detection of the Loss of a Wing for Underwater Gliders

Over the past five years, two of the Slocum underwater gliders operated by the UK National Oceanography Centre have lost a wing mid-mission without the pilot being aware of the problem until the point of vehicle retrieval. In this study, the steady-state data collected by gliders during the two deployments has been analysed to develop a fault detection system. From the data analysis, it is clear that the loss of the wing was a sudden event for both gliders. The main changes to the system dynamics associated with the event are an increase in the positive buoyancy of the glider and the occurrence of a roll angle on the side of the lost wing, with significant difference between dives and climbs. Hence, a simple effective system for the detection of the wing loss has been designed using the roll angle. Since sensors are known to fail and the roll sensor is non-critical to the operation of the glider, a back-up diagnostics system has been developed based on the dynamic model of the vehicle, capturing the change in buoyancy. Both systems are able to correctly detect the loss of the wing and notify pilots, who can re-plan missions to safely recover the vehicle

Transoral laser surgery for laryngeal carcinoma: has Steiner achieved a genuine paradigm shift in oncological surgery?

Transoral laser microsurgery applies to the piecemeal removal of malignant tumours of the upper aerodigestive tract using the CO2 laser under the operating microscope. This method of surgery is being increasingly popularised as a single modality treatment of choice in early laryngeal cancers (T1 and T2) and occasionally in the more advanced forms of the disease (T3 and T4), predomi- nantly within the supraglottis. Thomas Kuhn, the American physicist turned philosopher and historian of science, coined the phrase ‘paradigm shift’ in his groundbreaking book The Structure of Scientific Revolutions. He argued that the arrival of the new and often incompatible idea forms the core of a new paradigm, the birth of an entirely new way of thinking. This article discusses whether Steiner and col- leagues truly brought about a paradigm shift in oncological surgery. By rejecting the principle of en block resection and by replacing it with the belief that not only is it oncologically safe to cut through the substance of the tumour but in doing so one can actually achieve better results, Steiner was able to truly revolutionise the man- agement of laryngeal cancer. Even though within this article the repercussions of his insight are limited to the upper aerodigestive tract oncological surgery, his willingness to question other peoples’ dogma makes his contribution truly a genuine paradigm shift