Effects of Assistive Robot Behavior on Impressions of Patient Psychological Attributes: Vignette-Based Human-Robot Interaction Study.

BACKGROUND: As robots are increasingly designed for health management applications, it is critical to not only consider the effects robots will have on patients but also consider a patient's wider social network, including the patient's caregivers and health care providers, among others. OBJECTIVE: In this paper we investigated how people evaluate robots that provide care and how they form impressions of the patient the robot cares for, based on how the robot represents the patient. METHODS: We have used a vignette-based study, showing participants hypothetical scenarios describing behaviors of assistive robots (patient-centered or task-centered) and measured their influence on people's evaluations of the robot itself (emotional intelligence [EI], trustworthiness, and acceptability) as well as people's perceptions of the patient for whom the robot provides care. RESULTS: We found that for scenarios describing a robot that acts in a patient-centered manner, the robot will not only be perceived as having higher EI (P=.003) but will also cause people to form more positive impressions of the patient that the robot cares for (P<.001). We replicated and expanded these results to other domains such as dieting, learning, and job training. CONCLUSIONS: These results imply that robots could be used to enhance human-human relationships in the health care context and beyond.

BCScreen: A gene panel to test for breast carcinogenesis in chemical safety screening.

Targeted gene lists have been used in clinical settings to specify breast tumor type, and to predict breast cancer prognosis and response to treatment. Separately, panels have been curated to predict systemic toxicity and xenoestrogen activity as a part of chemical screening strategies. However, currently available panels do not specifically target biological processes relevant to breast development and carcinogenesis. We have developed a gene panel called the Breast Carcinogen Screen (BCScreen) as a tool to identify potential breast carcinogens and characterize mechanisms of toxicity. First, we used four seminal reviews to identify 14 key characteristics of breast carcinogenesis, such as apoptosis, immunomodulation, and genotoxicity. Then, using a hybrid data and knowledge-driven framework, we systematically combined information from whole transcriptome data from genomic databases, biomedical literature, the CTD chemical-gene interaction database, and primary literature review to generate a panel of 500 genes relevant to breast carcinogenesis. We used normalized pointwise mutual information (NPMI) to rank genes that frequently co-occurred with key characteristics in biomedical literature. We found that many genes identified for BCScreen were not included in prognostic breast cancer or systemic toxicity panels. For example, more than half of BCScreen genes were not included in the Tox21 S1500+ general toxicity gene list. Of the 230 that did overlap between the two panels, representation varied across characteristics of carcinogenesis ranging from 21% for genes associated with epigenetics to 82% for genes associated with xenobiotic metabolism. Enrichment analysis of BCScreen identified pathways and processes including response to steroid hormones, cancer, cell cycle, apoptosis, DNA damage and breast cancer. The biologically-based systematic approach to gene prioritization demonstrated here provides a flexible framework for creating disease-focused gene panels to support discovery related to etiology. With validation, BCScreen may also be useful for toxicological screening relevant to breast carcinogenesis.

Septic systems as sources of organic wastewater compounds in domestic drinking water wells in a shallow sand and gravel aquifer.

Domestic drinking water wells serve 44 million people in the US and are common globally. They are often located in areas served by onsite wastewater treatment systems, including septic systems, which can be sources of biological and chemical pollutants to groundwater. In this study we tested 20 domestic drinking water wells in a sand and gravel aquifer on Cape Cod, Massachusetts, USA, for 117 organic wastewater compounds (OWCs) and for inorganic markers of septic system impact. We detected 27 OWCs, including 12 pharmaceuticals, five per- and polyfluoroalkyl substances (PFASs), four organophosphate flame retardants, and an artificial sweetener (acesulfame). Maximum concentrations of several PFASs and pharmaceuticals were relatively high compared to public drinking water supplies in the US. The number of detected OWCs and total concentrations of pharmaceuticals and of PFASs were positively correlated with nitrate, boron, and acesulfame and negatively correlated with well depth. These wells were all located in areas served exclusively by onsite wastewater treatment systems, which are likely the main source of the OWCs in these wells, although landfill leachate may also be a source. Our results suggest that current regulations to protect domestic wells from pathogens in septic system discharges do not prevent OWCs from reaching domestic wells, and that nitrate, a commonly measured drinking water contaminant, is a useful screening tool for OWCs in domestic wells. Nitrate concentrations of 1mg/L NO3-N, which are tenfold higher than local background and tenfold lower than the US federal drinking water standard, were associated with wastewater impacts from OWCs in this study.

Parabens and Human Epidermal Growth Factor Receptor Ligand Cross-Talk in Breast Cancer Cells.

BACKGROUND: Xenoestrogens are synthetic compounds that mimic endogenous estrogens by binding to and activating estrogen receptors. Exposure to estrogens and to some xenoestrogens has been associated with cell proliferation and an increased risk of breast cancer. Despite evidence of estrogenicity, parabens are among the most widely used xenoestrogens in cosmetics and personal-care products and are generally considered safe. However, previous cell-based studies with parabens do not take into account the signaling cross-talk between estrogen receptor α (ERα) and the human epidermal growth factor receptor (HER) family. OBJECTIVES: We investigated the hypothesis that the potency of parabens can be increased with HER ligands, such as heregulin (HRG). METHODS: The effects of HER ligands on paraben activation of c-Myc expression and cell proliferation were determined by real-time polymerase chain reaction, Western blots, flow cytometry, and chromatin immunoprecipitation assays in ERα- and HER2-positive human BT-474 breast cancer cells. RESULTS: Butylparaben (BP) and HRG produced a synergistic increase in c-Myc mRNA and protein levels in BT-474 cells. Estrogen receptor antagonists blocked the synergistic increase in c-Myc protein levels. The combination of BP and HRG also stimulated proliferation of BT-474 cells compared with the effects of BP alone. HRG decreased the dose required for BP-mediated stimulation of c-Myc mRNA expression and cell proliferation. HRG caused the phosphorylation of serine 167 in ERα. BP and HRG produced a synergistic increase in ERα recruitment to the c-Myc gene. CONCLUSION: Our results show that HER ligands enhanced the potency of BP to stimulate oncogene expression and breast cancer cell proliferation in vitro via ERα, suggesting that parabens might be active at exposure levels not previously considered toxicologically relevant from studies testing their effects in isolation. CITATION: Pan S, Yuan C, Tagmount A, Rudel RA, Ackerman JM, Yaswen P, Vulpe CD, Leitman DC. 2016. Parabens and human epidermal growth factor receptor ligand cross-talk in breast cancer cells. Environ Health Perspect 124:563-569; http://dx.doi.org/10.1289/ehp.1409200.

Screening for Chemical Contributions to Breast Cancer Risk: A Case Study for Chemical Safety Evaluation.

BACKGROUND: Current approaches to chemical screening, prioritization, and assessment are being reenvisioned, driven by innovations in chemical safety testing, new chemical regulations, and demand for information on human and environmental impacts of chemicals. To conceptualize these changes through the lens of a prevalent disease, the Breast Cancer and Chemicals Policy project convened an interdisciplinary expert panel to investigate methods for identifying chemicals that may increase breast cancer risk. METHODS: Based on a review of current evidence, the panel identified key biological processes whose perturbation may alter breast cancer risk. We identified corresponding assays to develop the Hazard Identification Approach for Breast Carcinogens (HIA-BC), a method for detecting chemicals that may raise breast cancer risk. Finally, we conducted a literature-based pilot test of the HIA-BC. RESULTS: The HIA-BC identifies assays capable of detecting alterations to biological processes relevant to breast cancer, including cellular and molecular events, tissue changes, and factors that alter susceptibility. In the pilot test of the HIA-BC, chemicals associated with breast cancer all demonstrated genotoxic or endocrine activity, but not necessarily both. Significant data gaps persist. CONCLUSIONS: This approach could inform the development of toxicity testing that targets mechanisms relevant to breast cancer, providing a basis for identifying safer chemicals. The study identified important end points not currently evaluated by federal testing programs, including altered mammary gland development, Her2 activation, progesterone receptor activity, prolactin effects, and aspects of estrogen receptor ß activity. This approach could be extended to identify the biological processes and screening methods relevant for other common diseases.

Pharmaceuticals, perfluorosurfactants, and other organic wastewater compounds in public drinking water wells in a shallow sand and gravel aquifer.

Approximately 40% of U.S. residents rely on groundwater as a source of drinking water. Groundwater, especially unconfined sand and gravel aquifers, is vulnerable to contamination from septic systems and infiltration of wastewater treatment plant effluent. In this study, we characterized concentrations of pharmaceuticals, perfluorosurfactants, and other organic wastewater compounds (OWCs) in the unconfined sand and gravel aquifer of Cape Cod, Massachusetts, USA, where septic systems are prevalent. Raw water samples from 20 public drinking water supply wells on Cape Cod were tested for 92 OWCs, as well as surrogates of wastewater impact. Fifteen of 20 wells contained at least one OWC; the two most frequently-detected chemicals were sulfamethoxazole (antibiotic) and perfluorooctane sulfonate (perfluorosurfactant). Maximum concentrations of sulfamethoxazole (113 ng/L) and the anticonvulsant phenytoin (66 ng/L) matched or exceeded maximum reported concentrations in other U.S. public drinking water sources. The sum of pharmaceutical concentrations and the number of detected chemicals were both significantly correlated with nitrate, boron, and extent of unsewered residential and commercial development within 500 m, indicating that wastewater surrogates can be useful for identifying wells most likely to contain OWCs. Septic systems appear to be the primary source of OWCs in Cape Cod groundwater, although wastewater treatment plants and other sources were potential contributors to several wells. These results show that drinking water supplies in unconfined aquifers where septic systems are prevalent may be among the most vulnerable to OWCs. The presence of mixtures of OWCs in drinking water raises human health concerns; a full evaluation of potential risks is limited by a lack of health-based guidelines and toxicity assessments.

New exposure biomarkers as tools for breast cancer epidemiology, biomonitoring, and prevention: a systematic approach based on animal evidence.

BACKGROUND: Exposure to chemicals that cause rodent mammary gland tumors is common, but few studies have evaluated potential breast cancer risks of these chemicals in humans. OBJECTIVE: The goal of this review was to identify and bring together the needed tools to facilitate the measurement of biomarkers of exposure to potential breast carcinogens in breast cancer studies and biomonitoring. METHODS: We conducted a structured literature search to identify measurement methods for exposure biomarkers for 102 chemicals that cause rodent mammary tumors. To evaluate concordance, we compared human and animal evidence for agents identified as plausibly linked to breast cancer in major reviews. To facilitate future application of exposure biomarkers, we compiled information about relevant cohort studies. RESULTS: Exposure biomarkers have been developed for nearly three-quarters of these rodent mammary carcinogens. Analytical methods have been published for 73 of the chemicals. Some of the remaining chemicals could be measured using modified versions of existing methods for related chemicals. In humans, biomarkers of exposure have been measured for 62 chemicals, and for 45 in a nonoccupationally exposed population. The Centers for Disease Control and Prevention has measured 23 in the U.S. population. Seventy-five of the rodent mammary carcinogens fall into 17 groups, based on exposure potential, carcinogenicity, and structural similarity. Carcinogenicity in humans and rodents is generally consistent, although comparisons are limited because few agents have been studied in humans. We identified 44 cohort studies, with a total of > 3.5 million women enrolled, that have recorded breast cancer incidence and stored biological samples. CONCLUSIONS: Exposure measurement methods and cohort study resources are available to expand biomonitoring and epidemiology related to breast cancer etiology and prevention.

Temporal variability of urinary di(2-ethylhexyl) phthalate metabolites during a dietary intervention study.

Exposure to di(2-ethylhexyl) phthalate (DEHP) may be related to adverse health effects including developmental and reproductive disorders, prompting interest in strategies for reducing human exposure. We previously reported a reduction of DEHP metabolite levels in composite urine samples by more than 50% (geometric means) during a 3-day dietary intervention avoiding plastics in food packaging, preparation, and storage. In the present study, we analyzed individual spot urine samples before compositing in order to evaluate temporal variability. There were no meaningful changes in any of the previous findings when using individual rather than composited samples. Individual urine samples, like the composites, showed significant decreases of ≥50% in all three measured DEHP metabolites during the intervention. Compositing urine samples provided sufficient information to observe the effect of the intervention, whereas reducing analytical expenses compared with analyzing multiple samples individually. Low intraclass correlations (ICCs) for samples collected from the same person before the intervention indicate the importance of collecting multiple samples per exposure condition. Substantially larger ICCs during and after the intervention suggest that much of the variability observed in DEHP metabolite levels originates from dietary exposure.

Environmental exposures and mammary gland development: state of the science, public health implications, and research recommendations.

OBJECTIVES: Perturbations in mammary gland (MG) development may increase risk for later adverse effects, including lactation impairment, gynecomastia (in males), and breast cancer. Animal studies indicate that exposure to hormonally active agents leads to this type of developmental effect and related later life susceptibilities. In this review we describe current science, public health issues, and research recommendations for evaluating MG development. DATA SOURCES: The Mammary Gland Evaluation and Risk Assessment Workshop was convened in Oakland, California, USA, 16-17 November 2009, to integrate the expertise and perspectives of scientists, risk assessors, and public health advocates. Interviews were conducted with 18 experts, and seven laboratories conducted an MG slide evaluation exercise. Workshop participants discussed effects of gestational and early life exposures to hormonally active agents on MG development, the relationship of these developmental effects to lactation and cancer, the relative sensitivity of MG and other developmental end points, the relevance of animal models to humans, and methods for evaluating MG effects. SYNTHESIS: Normal MG development and MG carcinogenesis demonstrate temporal, morphological, and mechanistic similarities among test animal species and humans. Diverse chemicals, including many not considered primarily estrogenic, alter MG development in rodents. Inconsistent reporting methods hinder comparison across studies, and relationships between altered development and effects on lactation or carcinogenesis are still being defined. In some studies, altered MG development is the most sensitive endocrine end point. CONCLUSIONS: Early life environmental exposures can alter MG development, disrupt lactation, and increase susceptibility to breast cancer. Assessment of MG development should be incorporated in chemical test guidelines and risk assessment.

Food packaging and bisphenol A and bis(2-ethyhexyl) phthalate exposure: findings from a dietary intervention.

BACKGROUND: Bisphenol A (BPA) and bis(2-ethylhexyl) phthalate (DEHP) are high-production-volume chemicals used in plastics and resins for food packaging. They have been associated with endocrine disruption in animals and in some human studies. Human exposure sources have been estimated, but the relative contribution of dietary exposure to total intake has not been studied empirically. OBJECTIVES: To evaluate the contribution of food packaging to exposure, we measured urinary BPA and phthalate metabolites before, during, and after a "fresh foods" dietary intervention. METHODS: We selected 20 participants in five families based on self-reported use of canned and packaged foods. Participants ate their usual diet, followed by 3 days of "fresh foods" that were not canned or packaged in plastic, and then returned to their usual diet. We collected evening urine samples over 8 days in January 2010 and composited them into preintervention, during intervention, and postintervention samples. We used mixed-effects models for repeated measures and Wilcoxon signed-rank tests to assess change in urinary levels across time. RESULTS: Urine levels of BPA and DEHP metabolites decreased significantly during the fresh foods intervention [e.g., BPA geometric mean (GM), 3.7 ng/mL preintervention vs. 1.2 ng/mL during intervention; mono-(2-ethyl-5-hydroxy hexyl) phthalate GM, 57 ng/mL vs. 25 ng/mL]. The intervention reduced GM concentrations of BPA by 66% and DEHP metabolites by 53-56%. Maxima were reduced by 76% for BPA and 93-96% for DEHP metabolites. CONCLUSIONS: BPA and DEHP exposures were substantially reduced when participants' diets were restricted to food with limited packaging.