Estrogenic activity of phenolic additives determined by an in vitro yeast bioassay

Copyright @ 2001 Environmental Health PerspectivesWe used a recombinant yeast estrogen assay to assess the activity of 73 phenolic additives that are used as sunscreens, preservatives, disinfectants, antioxidants, flavorings, or for perfumery. Thirty-two of these compounds displayed activity: 22 with potencies relative to 17 beta -estradiol, ranging from 1/3,000 to -estradiol. Forty-one compounds were inactive. The major criteria for activity appear to be the presence of an unhindered phenolic OH group in a para position and a molecular weight of 140-250 Da.This work was supported in part under contract with the U.K. Department of Trade and Industry as part of the Government Chemist Programme

Re-evaluation of the first synthetic estrogen, 1-keto-1,2,3,4-tetrahydrophenanthrene, and bisphenol A, using both the ovariectomised rat model used in 1933 and additional assays

1-Keto-1,2,3,4-tetrahydrophenanthrene (THP-1) was reported by Cook et al in 1933 as the first synthetic estrogen. Estrogenic activity was assessed by the induction of vaginal cornification in ovariectomised rats. The corresponding 4-isomer (THP-4) was shown to be inactive. Both chemicals have been re-synthesised and assessed for hormonal activity. Each chemical bound weakly and to the same extent to isolated estrogen receptors, but only at high concentrations. However, they each lacked estrogenic or anti-estrogenic activity when evaluated in vitro using a yeast hER assay, and both failed to induce vaginal cornification or uterotrophic effects in ovariectomised rats. THP-1, and to a lesser extent THP-4, were shown to possess weak androgenic and anti-androgenic activity in vitro when evaluated using an hAR yeast assay. Estrogenic activity for bisphenol A (BPA) was subsequently demonstrated by Dodds and Lawson (1936) using the same ovariectomised rat protocol, and this activity has been confirmed and supplemented by positive uterotrophic effects for BPA in the same bioassays. The present results illustrate the complexity of deriving conclusions regarding the hormonal activities of chemicals. First, some activities observed in isolated hormonal receptor binding assays may not be expressed in functional hormonal assays. This indicates the need for functional hormonal assays in any screening programme. Second, that activities observed for a chemical in one hormonal assay may not be reflected in related hormonal assays. This indicates the need to define assay protocols with some precision when incorporating them into screening batteries. Finally, that some literature reports of hormonal activity for chemicals may not be capable of independent confirmation under apparently identical conditions of test. This illustrates the need to use lists of hormonally active chemicals with car

Understanding bricolage in norm development: South Africa, the International Criminal Court, and the contested politics of transitional justice

Within international relations the normative agency of African actors is often downplayed or derided. This article develops the concept of bricolage to offer a novel understanding of norm development and contestation in international relations, including the role African actors play in this. We contend that a norm's core hypothesis can be thought of as the nucleus of a norm. In the case of complex international norms, if this core hypothesis is sufficiently vague and malleable, the norm will continue to attract a range of actors who may claim to share a commitment to enacting the core hypothesis even if they simultaneously promote a variety of potentially conflicting and contradictory meanings-in-use of the norm when doing so. Each meaning-in-use, we argue, might be thought of as a product of bricolage: a process of combining and adapting both new and second-hand materials, knowledges, values, and practices by an actor to address a problem in hand. Through a detailed study of the contestation of transitional justice between South Africa and the International Criminal Court, we elucidate how bricolage can help to illuminate the normative agency of African actors in shaping transitional justice. Processes of bricolage add complexity and potentially confusion to a norm's development, but bricolage also offers the potential for a creative and dynamic means by which a range of actors can inject pluralism, dexterity, and vitality into debates about a norm's meaning and operationalisation

The Prevalence and Control of Bacillus and Related Spore-Forming Bacteria in the Dairy Industry

peer-reviewedMilk produced in udder cells is sterile but due to its high nutrient content, it can be a good growth substrate for contaminating bacteria. The quality of milk is monitored via somatic cell counts and total bacterial counts, with prescribed regulatory limits to ensure quality and safety. Bacterial contaminants can cause disease, or spoilage of milk and its secondary products. Aerobic spore-forming bacteria, such as those from the genera Sporosarcina, Paenisporosarcina, Brevibacillus, Paenibacillus, Geobacillus and Bacillus, are a particular concern in this regard as they are able to survive industrial pasteurization and form biofilms within pipes and stainless steel equipment. These single or multiple-species biofilms become a reservoir of spoilage microorganisms and a cycle of contamination can be initiated. Indeed, previous studies have highlighted that these microorganisms are highly prevalent in dead ends, corners, cracks, crevices, gaskets, valves and the joints of stainless steel equipment used in the dairy manufacturing plants. Hence, adequate monitoring and control measures are essential to prevent spoilage and ensure consumer safety. Common controlling approaches include specific cleaning-in-place processes, chemical and biological biocides and other novel methods. In this review, we highlight the problems caused by these microorganisms, and discuss issues relating to their prevalence, monitoring thereof and control with respect to the dairy industry.NG is funded by the Teagasc Walsh Fellowship Scheme and through the Irish Dairy Levy funded project ‘Thermodur-Out.

Linkages Between the Phenologies of Jack Pine \u3ci\u3e(Pinus Banksiana)\u3c/i\u3e Foliage and Jack Pine Budworm (Lepidoptera: Tortricidae)

A field study conducted in 2001 and 2002 in the Michigan Upper Peninsula investigated seasonal associations between the development of jack pine, Pinus banksiana Lamb., and larvae of the jack pine budworm Choristoneura pinus Freeman (Lepidoptera: Tortricidae). There was almost no active relationship between post-diapause emerging second instars and elongation of vegetative shoots. Early instars were not closely synchronized with the flushing of current-year needle fascicles, which is required to optimize larval feeding. How- ever, there were close feeding and shelter relationships between early instars and year-2 pollen cone development. Associations with, and larval damage to, year-2 seed cones were dependent upon larval population size and posed only minimal and periodic threats to jack pine seed production. As a consequence, early instar jack pine budworm relied almost exclusively on pollen cones for survival. Third to fifth instars vacated pollen cones as soon as they became desiccated. Only then did these larvae start close associations with vegetative shoots. First, they excised partially emerged needles at their base, and when the needle-pairs completely escaped their fascicle sheath, the larvae fed routinely on the complete needle lamina. Late instars, pupae and adults were associated with previous years’ and current-year foliage without any apparent bias. This study has shown that it might be more practical to time insecticide strategies, which are intended to manage jack pine budworm larvae, to the tree’s phenology rather than jack pine budworm larval indices

The rodent uterotrophic assay: Critical protocol features, studies with nonyl phenols, and comparison with a yeast estrogenicity assay

The major protocol features of the immature rat uterotrophic assay have been evaluated using a range of reference chemicals. The protocol variables considered include the selection of the test species and route of chemical administration, the age of the test animals, the maintenance diet used, and the specificity of the assay for estrogens. It is concluded that three daily oral administrations of test chemicals to 21- to 22-day-old rats, followed by determination of absolute uterus weights on the fourth day, provide a sensitive and toxicologically relevant in vivo estrogenicity assay. Rats are favored over mice for reasons of toxicological practice, but the choice of test species is probably not a critical protocol variable, as evidenced by the similar sensitivity of rats and mice to the uterotrophic activity of methoxychlor. Vaginal opening is shown to be a useful, but nondefinitive, adjunct to the uterotrophic assay. The ability of test chemicals to reduce or abolish the uterotrophic response of estradiol is suggested to provide a useful extension of the uterotrophic assay for the purpose of detecting antiestrogens. The results of a series of studies on the environmental estrogen nonyl phenol (NP), and its linear isomer n -nonyl phenol, confirm that branching of the aliphatic side chain is important for activity. 17beta-Desoxyestradiol is shown to be of similar activity to estradiol in the uterotrophic assay and is suggested to represent the "parent" estrogen of NP. Benzoylation of NP and 17-desoxyestradiol did not affect their uterotrophic activity, in contrast to the enhancing effect of benzoylation on estradiol. Selected chemicals shown to be active in the immature rat uterotrophic assay were also evaluated in an in vitro yeast human estrogen receptor transactivation assay. Most of the chemicals gave similar qualitative responses to those seen in the uterotrophic assay, and the detection of the estrogen methoxychlor by the yeast assay evidenced a degree of intrinsic metabolic competence. However, the assay had a reduced ability (compared to rodents) to hydrolyze the benzoate ester of estradiol, and the estrogenic benzoate derivative of NP was not active in the yeast assay. These last results indicate that current metabolic deficiencies of in vitro estrogenicity assays will limit the value of negative data for the immediate future. The results described illustrate the intrinsic complexity of evaluating chemicals for estrogenic activities and confirm the need for rigorous attention to experimental design and criteria for assessing estrogenic activity

Working with Children with Learning Disabilities and/or who Communicate Non-verbally: Research experiences and their implications for social work education, increased participation and social inclusion

Social exclusion, although much debated in the UK, frequently focuses on children as a key 'at risk' group. However, some groups, such as disabled children, receive less consideration. Similarly, despite both UK and international policy and guidance encouraging the involvement of disabled children and their right to participate in decision-making arenas, they are frequently denied this right. UK based evidence suggests that disabled children's participation lags behind that of their non-disabled peers, often due to social work practitioners' lack of skills, expertise and knowledge on how to facilitate participation. The exclusion of disabled children from decision-making in social care processes echoes their exclusion from participation in society. This paper seeks to begin to address this situation, and to provide some examples of tools that social work educators can introduce into pre- and post-qualifying training programmes, as well as in-service training. The paper draws on the experiences of researchers using non-traditional qualitative research methods, especially non-verbal methods, and describes two research projects, focusing on the methods employed to communicate with and involve disabled children, the barriers encountered and lessons learnt. Some of the ways in which these methods of communication can inform social work education are explored alongside wider issues of how and if increased communication can facilitate greater social inclusion

Estimating The Costs And Cost-effectiveness Of Promoting Mammography Screening Among US-based Latinas

Purpose: We characterize the costs and cost-effectiveness of a community health worker (CHW)-based intervention to promote screening mammography among US-based non-adherent Latinas. Methods: The parent study was a randomized controlled trial for 536 Latinas aged 42-74 years old who had sought care within a safety net health center in Western Washington. Participants were block-randomized within clinic to the control arm (usual care) or intervention arm (CHW-led motivational interviewing intervention). We used the perspective of the organization implementing promotional activities to characterize costs and cost-effectiveness. Cost data were categorized as program set-up and maintenance (initial training, booster/annual training) program implementation (administrative activities, intervention delivery); and, overhead/miscellaneous expenses. Cost-effectiveness was calculated as the incremental cost of screening for each additional woman screened between the intervention and control arms. Results: The respective costs per participant for standard care and the intervention arm were $69.96 and$300.99. There were no study arm differences in 1-year QALYs among women who completed a 12-month follow-up survey (intervention= 0.8827, standard care = 0.8841). Most costs pertained to program implementation and administrative activities specifically. The incremental cost per additional woman screened was $2,595.32. Conclusions: Our findings are within the ranges of costs and cost-effectiveness for other CHW programs to promote screening mammography among underserved populations. Our strong study design and focus on non-adherent women provides important strengths to this body of work, especially give implementation and dissemination science efforts regarding CHW-based health promotion for health disparity populations

Quantifying Privacy Loss of Human Mobility Graph Topology

Human mobility is often represented as a mobility network, or graph, with nodes representing places of significance which an individual visits, such as their home, work, places of social amenity, etc., and edge weights corresponding to probability estimates of movements between these places. Previous research has shown that individuals can be identified by a small number of geolocated nodes in their mobility network, rendering mobility trace anonymization a hard task. In this paper we build on prior work and demonstrate that even when all location and timestamp information is removed from nodes, the graph topology of an individual mobility network itself is often uniquely identifying. Further, we observe that a mobility network is often unique, even when only a small number of the most popular nodes and edges are considered. We evaluate our approach using a large dataset of cell-tower location traces from 1 500 smartphone handsets with a mean duration of 430 days. We process the data to derive the top−N places visited by the device in the trace, and find that 93% of traces have a unique top−10 mobility network, and all traces are unique when considering top−15 mobility networks. Since mobility patterns, and therefore mobility networks for an individual, vary over time, we use graph kernel distance functions, to determine whether two mobility networks, taken at different points in time, represent the same individual. We then show that our distance metrics, while imperfect predictors, perform significantly better than a random strategy and therefore our approach represents a significant loss in privacy