A Role for TGFβ Signaling in Preclinical Osteolytic Estrogen Receptor-Positive Breast Cancer Bone Metastases Progression

While tumoral Smad-mediated transforming growth factor β (TGFβ) signaling drives osteolytic estrogen receptor α-negative (ER-) breast cancer bone metastases (BMETs) in preclinical models, its role in ER+ BMETs, representing the majority of clinical BMETs, has not been documented. Experiments were undertaken to examine Smad-mediated TGFβ signaling in human ER+ cells and bone-tropic behavior following intracardiac inoculation of estrogen (E₂)-supplemented female nude mice. While all ER+ tumor cells tested (ZR-75-1, T47D, and MCF-7-derived) expressed TGFβ receptors II and I, only cells with TGFβ-inducible Smad signaling (MCF-7) formed osteolytic BMETs in vivo. Regulated secretion of PTHrP, an osteolytic factor expressed in >90% of clinical BMETs, also tracked with osteolytic potential; TGFβ and E₂ each induced PTHrP in bone-tropic or BMET-derived MCF-7 cells, with the combination yielding additive effects, while in cells not forming BMETs, PTHrP was not induced. In vivo treatment with 1D11, a pan-TGFβ neutralizing antibody, significantly decreased osteolytic ER+ BMETs in association with a decrease in bone-resorbing osteoclasts at the tumor-bone interface. Thus, TGFβ may also be a driver of ER+ BMET osteolysis. Moreover, additive pro-osteolytic effects of tumoral E₂ and TGFβ signaling could at least partially explain the greater propensity for ER+ tumors to form BMETs, which are primarily osteolytic.     

Effect characterization in social impact assessment: a scan of current practice

Good-practice guidance for impact assessment (IA) consistently recommends that IA practitioners characterize impacts using parameters such as magnitude, likelihood and geographic extent. In practice, however, this guidance is not always followed. In order to identify the extent to which impacts are characterized for social topics, this paper reviewed of the social assessment sections of 57 environmental impact assessment (EIA) reports from 12 countries. The review found that 61% attempted to characterize impacts for social topics, while 39% did not. Of the 61% that characterized impacts, just over half (54%) provided transparent definitions for effect levels (e.g. low, medium and high). The research results shine a light on the lack of consistency in thoroughly, appropriately and transparently characterizing social effects. Advancing this discussion amongst SIA professionals is important, as it will benefit the quality of SIAs and mitigation approaches in the future. Finally, this paper puts forward a proposed model for social effect characterization parameters that can be used and adapted for future assessments.

Abbreviation: EIA: environmental impact assessment; IA: impact assessment; SIA: socio-economic impact assessment.     

Feeling safe and comfortable in the urban environment

Safety is recognised as an important goal of urban regeneration projects and implementing the principles of Crime Prevention Through Environmental Design (CPTED) has been proposed as one way of enhancing community safety. Yet there are few critiques of how effective CPTED is in achieving this. This paper reports on a pilot study that explores the link between CPTED principles and people’s feelings of safety and comfort in an urban precinct of Adelaide, South Australia. The research combines a micro-scale analysis of the built environment and a series of interviews with people who live and/or work in the area. The research highlights the importance of some of the CPTED principles including activity, maintenance, sight lines but also reveals the importance of familiarity and personal safety strategies.     

Ventilation and posture effects on inhalation exposures to volatile cleaning ingredients in a simulated domestic worker cleaning environment

Associations between cleaning chemical exposures and asthma have previously been identified in professional cleaners and healthcare workers. Domestic workers, including housecleaners and caregivers, may receive similar exposures but in residential environments with lower ventilation rates. Study objectives were to compare exposures to occupational exposure limits (OELs), to determine relative contributions from individual cleaning tasks to overall exposure, and to evaluate the effects of ventilation and posture on exposure. Airborne chemical concentrations of sprayed cleaning chemicals (acetic acid or ammonia) were measured during typical cleaning tasks in a simulated residential work environment. Whole-house cleaning exposures (18 cleaning tasks) were measured using integrated personal sampling methods. Individual task exposures were measured with a sampling line attached to subjects' breathing zones, with readings recorded by a ppbRAE monitor, equipped with a photoionization detector calibrated for ammonia and acetic acid measurements. Integrated sampling results indicated no exposures above OELs occurred, but 95th percentile air concentrations would require risk management decisions. Exposure reductions were observed with increased source distance, with lower exposures from mopping floors compared to kneeling. Exposure reductions were also observed for most but not all tasks when ventilation was used, with implications that alternative exposure reduction methods may be needed.     

Poly(ethylene glycol)s 2000-8000 in water may be planar: A small-angle neutron scattering (SANS) structure study

Poly(ethylene glycol)s of all molecular weights are highly soluble in water. Small-Angle Neutron Scattering (SANS) data has been collected on buffered ionic D₂O solutions of PEGs of nominal molecular weights 2000, 4000, and 8000 Da at a low concentration of 0.5% (w/v). The radii of gyration R_g vary as approximately M_w^0.5, which is consistent with both a Gaussian chain and a flat plate. Numerous types of experiments indicate flaws in the interpretation as a Gaussian chain. When the alternative interpretation is used, the structures in these dilute solutions are found to have a constant area stoichiometry of 1:1 water:-CH₂CH₂O- and are consistent with the data when monomeric molecules are plates of packed chains one chain thick.