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

U.S. Mexican relations: a comprehensive review on heroin supply and demand

As an ever-increasing heroin epidemic pervades the cities and suburbs of America, attempts to tackle the issue have taken prominence in the White House. To fight the ‘war on drugs’ an in depth understanding of the process of production, heroin trafficking routes and previous political policy failures is required. This review focuses on how the production of Mexican heroin dominates the U.S. illicit drug market. A comprehensive analysis of current and previous legislation on drug laws and security regulations at the U.S Mexican border provides suggestions for future policies aimed at tackling the heroin problem in the U.S. Issues explored in this review are; the increased Mexican opium production stemming from the legalisation of marijuana, which shifted Mexican farmers to opium cultivation, the underlying parameters of poverty in Mexico and cartel influenced corruption of government within Mexico. This review suggests that Mexico alone cannot be blamed for the U.S. heroin problem, although it is sole supplier, there must be a demand for the supply within U.S. society. The main reason for the expansion of the heroin epidemic sweeping the streets of the U.S. is the increase in painkiller addition within U.S. society. This coupled with lower cost of heroin on the illicit market may lead many users to replace pain killer cravings with heroin. This poses the question ‘is it realistic to completely remove the heroin problem from the U.S. through the elimination of trafficking routes and by reforming previous failed policies or would drug trafficking organisations alter the structure of their businesses and routes to adapt to any change in policy

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 cytogenetic screening of South African artificial insemination bulls

International audienc

The recent introduction of a 1/29 chromosome translocation in South African Brahman cattle

International audienc

A 1/29 chromosome translocation in Southern African Nguni cattle. The identification, occurrence and origin of the translocation

International audienc

Plate-impact loading of cellular structures formed by selective laser melting

Studies of the shock loading of porous material have the potential to improve our understanding of factors such as density, crush strength and pore size on energy absorbing capability. Porous components were manufactured using Selective Laser Melting (SLM) in which layers of metal powder are fused together to create a structure specified by an electronic file. Samples have been manufactured in which a lattice is formed by an array of intersecting rods angled at 45 degrees to the surface of a 6 mm thick x ~100 mm diameter disc. The cell size is 1 mm3 and the density is 44.6% of solid. A 100 mm gas gun has been used to impact the porous samples onto solid stainless steel plates. Het-V laser interferometry was used to measure the velocity vs. time profile of the transmitted shock. The experimental results were compared with three dimensional computer predictions. It was found that the simulations reproduced the main features of the experimental record but tended to underestimate the measured velocities, suggesting that the codes were not calculating the energy absorbed by the lattice correctly. Additional calculations were performed with the aim of building a picture of the processes of energy absorption in cellular materials whose structure is varied systematically. These supporting studies suggest a possible explanation for the observed computational/experimental discrepancies. © 2012 British Crown

Assisted Probe Positioning for Ultrasound Guided Radiotherapy Using Image Sequence Classification

Effective transperineal ultrasound image guidance in prostate external beam radiotherapy requires consistent alignment between probe and prostate at each session during patient set-up. Probe placement and ultrasound image interpretation are manual tasks contingent upon operator skill, leading to interoperator uncertainties that degrade radiotherapy precision. We demonstrate a method for ensuring accurate probe placement through joint classification of images and probe position data. Using a multi-input multi-task algorithm, spatial coordinate data from an optically tracked ultrasound probe is combined with an image classifier using a recurrent neural network to generate two sets of predictions in real-time. The first set identifies relevant prostate anatomy visible in the field of view using the classes: outside prostate, prostate periphery, prostate centre. The second set recommends a probe angular adjustment to achieve alignment between the probe and prostate centre with the classes: move left, move right, stop. The algorithm was trained and tested on 9,743 clinical images from 61 treatment sessions across 32 patients. We evaluated classification accuracy against class labels derived from three experienced observers at 2/3 and 3/3 agreement thresholds. For images with unanimous consensus between observers, anatomical classification accuracy was 97.2% and probe adjustment accuracy was 94.9%. The algorithm identified optimal probe alignment within a mean (standard deviation) range of 3.7° (1.2°) from angle labels with full observer consensus, comparable to the 2.8° (2.6°) mean interobserver range. We propose such an algorithm could assist radiotherapy practitioners with limited experience of ultrasound image interpretation by providing effective real-time feedback during patient set-up

Validating self-report of diabetes use by participants in the 45 and up study: A record linkage study

Background: Prevalence studies usually depend on self-report of disease status in survey data or administrative data collections and may over- or under-estimate disease prevalence. The establishment of a linked data collection provided an opportunity to explore the accuracy and completeness of capture of information about diabetes in survey and administrative data collections. Methods. Baseline questionnaire data at recruitment to the 45 and Up Study was obtained for 266,848 adults aged 45 years and over sampled from New South Wales, Australia in 2006-2009, and linked to administrative data about hospitalisation from the Admitted Patient Data Collection (APDC) for 2000-2009, claims for medical services (MBS) and pharmaceuticals (PBS) from Medicare Australia data for 2004-2009. Diabetes status was determined from response to a question 'Has a doctor EVER told you that you have diabetes' (n = 23,981) and augmented by examination of free text fields about diagnosis (n = 119) or use of insulin (n = 58). These data were used to identify the sub-group with type 1 diabetes. We explored the agreement between self-report of diabetes, identification of diabetes diagnostic codes in APDC data, claims for glycosylated haemoglobin (HbA1c) in MBS data, and claims for dispensed medication (oral hyperglycaemic agents and insulin) in PBS data. Results: Most participants with diabetes were identified in APDC data if admitted to hospital (79.3%), in MBS data with at least one claim for HbA1c testing (84.7%; 73.4% if 2 tests claimed) or in PBS data through claim for diabetes medication (71.4%). Using these alternate data collections as an imperfect 'gold standard' we calculated sensitivities of 83.7% for APDC, 63.9% (80.5% for two tests) for MBS, and 96.6% for PBS data and specificities of 97.7%, 98.4% and 97.1% respectively. The lower sensitivity for HbA1c may reflect the use of this test to screen for diabetes suggesting that it is less useful in identifying people with diabetes without additional information. Kappa values were 0.80, 0.70 and 0.80 for APDC, MBS and PBS respectively reflecting the large population sample under consideration. Compared to APDC, there was poor agreement about identifying type 1 diabetes status. Conclusions: Self-report of diagnosis augmented with free text data indicating diabetes as a chronic condition and/or use of insulin among medications used was able to identify participants with diabetes with high sensitivity and specificity compared to available administrative data collections. © 2013 Comino et al.; licensee BioMed Central Ltd

The effects of two weeks high-intensity interval training on fasting glucose, glucose tolerance and insulin resistance in adolescent boys: a pilot study

This is the final version. Available on open access from BMC via the DOI in this recordAvailability of data and materials: The datasets generated and analysed during the current study are not publicly available due to ethical restrictions but are available from the corresponding author upon reasonable request.Background Current evidence of metabolic health benefits of high-intensity interval training (HIIT) are limited to longer training periods or conducted in overweight youth. This study assessed 1) fasting and postprandial insulin and glucose before and after 2 weeks of HIIT in healthy adolescent boys, and 2) the relationship between pre intervention health outcomes and the effects of the HIIT intervention. Methods Seven healthy boys (age:14.3 ± 0.3 y, BMI: 21.6 ± 2.6, 3 participants classified as overweight) completed 6 sessions of HIIT over 2 weeks. Insulin resistance (IR) and blood glucose and insulin responses to a Mixed Meal Tolerance Test (MMTT) were assessed before (PRE), 20 h and 70 h after (POST) the final HIIT session. Results Two weeks of HIIT had no effect on fasting plasma glucose, insulin or IR at 20 h and 70 h POST HIIT, nor insulin and glucose response to MMTT (all P > 0.05). There was a strong negative correlation between PRE training IR and change in IR after HIIT (r = − 0.96, P < 0.05). Conclusion Two weeks of HIIT did not elicit improvements to fasting or postprandial glucose or insulin health outcomes in a group of adolescent boys. However the negative correlation between PRE IR and improvements after HIIT suggest that interventions of this type may be effective in adolescents with raised baseline IR.National Institute for Health Research (NIHR)Northcott Devon Medical Foundatio