Governance of environmental risk: New approaches to managing stakeholder involvement

Disputes concerning industrial legacies such as the disposal of toxic wastes illustrate changing pressures on corporations and governments. Business and governments are now confronted with managing the expectations of a society increasingly aware of the social and environmental impacts and risks associated with economic development and demanding more equitable distribution and democratic management of such risks. The closed managerialist decision-making of the powerful bureaucracies and corporations of the industrial era is informed by traditional management theory which cannot provide a framework for the adequate governance of these risks. Recent socio-political theories have conceptualised some key themes that must be addressed in a more fitting approach to governance. We identify more recent management and governance theory which addresses these themes and develop a process-based approach to governance of environmental disputes that allows for the evolving nature of stakeholder relations in a highly complex multiple stakeholder arena. © 2008 Elsevier Ltd. All rights reserved

Estrogen and progesterone induce persistent increases in p53-dependent apoptosis and suppress mammary tumors in BALB/c-Trp53+/- mice

INTRODUCTION Treatment with estrogen and progesterone (E+P) mimics the protective effect of parity on mammary tumors in rodents and depends upon the activity of p53. The following experiments tested whether exogenous E+P primes p53 to be more responsive to DNA damage and whether these pathways confer resistance to mammary tumors in a mouse model of Li-Fraumeni syndrome. METHODS Mice that differ in p53 status (Trp53+/+, Trp53+/-, Trp53-/-) were treated with E+P for 14 days and then were tested for p53-dependent responses to ionizing radiation. Responses were also examined in parous and age-matched virgins. The effects of hormonal exposures on tumor incidence were examined in BALB/c-Trp53+/- mammary tissues. RESULTS Nuclear accumulation of p53 and apoptotic responses were increased similarly in the mammary epithelium from E+P-treated and parous mice compared with placebo and age-matched virgins. This effect was sustained for at least 7 weeks after E+P treatment and did not depend on the continued presence of ovarian hormones. Hormone stimulation also enhanced apoptotic responses to ionizing radiation in BALB/c-Trp53+/- mice but these responses were intermediate compared with Trp53+/+ and Trp-/- tissues, indicating haploinsufficiency. The appearance of spontaneous mammary tumors was delayed by parity in BALB/c-Trp53+/- mice. The majority of tumors lacked estrogen receptor (ER), but ER+ tumors were observed in both nulliparous and parous mice. However, apoptotic responses to ionizing radiation and tumor incidence did not differ among outgrowths of epithelial transplants from E+P-treated donors and nulliparous donors. CONCLUSION Therefore, E+P and parity confer a sustained increase in p53-mediated apoptosis within the mammary epithelium and suppress mammary tumorigenesis, but this effect was not retained in epithelial outgrowths.This work was supported by grants from the US Army Medical Research and Materiel Command (W81XWH0410385 to KAD and DAMD17-01-1-0315 to ACB) and the National Institutes of Health (RO1-CA095164 to DJJ)

Oxybenzone Alters Mammary Gland Morphology in Mice Exposed During Pregnancy and Lactation

Hormones and endocrine-disrupting chemicals are generally thought to have permanent “organizational” effects when exposures occur during development but not adulthood. Yet, an increasing number of studies have shown that pregnant females are disrupted by endocrine-disrupting chemical exposures, with some effects that are permanent. Here, we examined the long-term effects of exposure to oxybenzone, an estrogenic chemical found in sunscreen and personal care products, on the morphology of the mammary gland in mice exposed during pregnancy and lactation. Female mice were exposed to vehicle or 30, 212, or 3000 µg oxybenzone/kg/d, from pregnancy day 0 until weaning. A nulliparous group, receiving vehicle treatment, was also evaluated. Mammary glands were collected 5 weeks after involution for whole-mount, histological, immunohistochemical, and molecular analyses. Exposure to 3000 µg oxybenzone/kg/d induced permanent changes to ductal density that was significantly different from both the nulliparous and vehicle groups. The two highest doses of oxybenzone similarly induced an intermediate phenotype for expression of progesterone receptor. A monotonic, dose-dependent increase in cell proliferation was also observed in the oxybenzone-treated females, becoming statistically significant at the highest dose. Finally, oxybenzone exposure induced an intermediate phenotype for Esr1 expression in all oxybenzone-treated groups. These data suggest that oxybenzone, at doses relevant to human exposures, produces long-lasting alterations to mammary gland morphology and function. Further studies are needed to determine if exposure to this chemical during pregnancy and lactation will interfere with the known protection that pregnancy provides against breast cancer

Electronic Footprints in the Sand: Technologies for Assisting Domestic Violence Survivors

With the rapid growth and spread of Internet-based social support systems, the impact that these systems can make to society – be it good or bad – has become more significant and can make a real difference to people’s lives. As such, various aspects of these systems need to be carefully investigated and analysed, including their security/privacy issues. In this paper, we present our work in designing and implementing various technological features that can be used to assist domestic violence survivors in obtaining help without leaving traces which might lead to further violence from their abuser. This case study serves as the core of our paper, in which we outline our approach, various de- sign considerations – including difficulties in keeping browsing history private, our currently implemented solutions (single use URL, targeted history sanitita- tion agent, and secret graphical gateway), as well as novel ideas for future work (including location-based service advertising and deployment in the wild)

Gamma-ray observations of the Crab Region using a coded-aperture telescope

The region of the Galactic anticenter, including the Crab Nebula, was observed during a balloon flight of the University of New Hampshire Directional Gamma-Ray Telescope employing the coded-aperture imaging technique to image celestial gamma-radiation between 160 keV and 9.3 MeV. The background systematics are treated with a simple and relatively straightforward correction procedure. The results demonstrate that the coded-aperture procedure is a viable approach for imaging not only point sources of radiation, but also extended sources of emission. The results for the Crab\u27s photon spectrum are consistent with a power-law spectrum. Upper limits on the flux levels of line emission at 405 keV and 1050 keV and on the flux from the X-ray binary source A0535 + 26 and diffuse Galactic emission from the anticenter region are derived

Gamma-ray observations of Cygnus X-1 and Cygnus X-3 using a coded-aperture telescope

A balloon-borne coded-aperture telescope, measuring gamma-ray photons in the 160 keV to 9.3 MeV range, was used to observe the Cygnus region of the sky on October 1 and 2, 1984. In the 2-9.3-MeV band, evidence is found for a hard spectral component with a mean flux level at the top of the atmosphere of 7.4 + or - 2.5 x 10 to the -7th photons/sq cm per s per keV, inconsistent with the predictions of the inverse Compton models normally used to describe the X-ray emission. Both Cyg X-1 and Cyg X-3 could be observed simultaneously with the telescope. The results are used to establish 1-sigma upper flux limits on the spectral emission from Cyg X-3

Activin Limits Progenitor Capability by Promoting Epithelial Cell Differentiation in the Mammary Gland

Transforming growth factor beta (TGF-beta) and activin utilize common signaling pathways, via smad2/3 and smad4, to mediate tumor suppression by effecting cell cycle arrest and apoptosis. Differences in temporal expression patterns suggest that each cytokine has specific roles in mammary gland development. Activin is expressed during pregnancy and lactation and is required for branching and lactogenesis, implying a role in mammary gland maturation. In contrast, TGF-beta is expressed during involution during mammary gland regression and functions to re-organize the mammary epithelial content to the non-lactating state. Previously, we found that TGF-beta and activin do share common signaling pathways allowing both cytokines to restrict the growth of mammary epithelial cells. However, extended exposure to TGF-beta (5ng/ml; 14 days) causes epithelial to mesencymal transition (EMT). The TGF-beta-treated cells were de-differentiated with loss of both luminal and basal markers. Activin treatment (50ng/ml; 14 days) did not activate EMT. Rather, activin promotes luminal epithelial differentiation with increased expression of prolactin receptor and luminal keratins. Therefore, to test the hypothesis that activin-treatment promotes luminal differentiation and decreases the proportion of progenitor cells in the epithelial population, we compared mammosphere forming capability in vitro and performed limiting dilution experiments in vivo by transplanting 50,000 or 500,000 pre-treated cells into cleared mouse mammary fat pads. The mammosphere assay showed that secondary mammospheres were significantly decreased in the activin-treated cells compared to both the control and TGF-beta treated cells. Tumor incidence between activin-treated and control cells were similar for transplants of 50,000 cells, but tumor incidence was significantly greater in TGF-beta-treated transplants. However, the activin-treated cells had poor outgrowth potential at both 50,000 and 500,000 cells relative to control. We conclude that activin may have the potential to reduce the stem cell population by promoting epithelial cell differentiation

Dose-response relationship of ICS/fast-onset LABA as reliever therapy in asthma

The dose-response relationship of inhaled corticosteroid (ICS)/fast-onset long acting beta agonist (LABA) reliever therapy has not been formally addressed. The objective of this retrospective analysis is to ascertain from the available evidence whether ICS/fast-onset LABA administered as reliever therapy has a different dose-response relationship than maintenance fixed dose ICS/fast-onset LABA therapy in reducing risk of severe exacerbations