Quantifying engineered nanomaterial toxicity: comparison of common cytotoxicity and gene expression measurements

BACKGROUND: When evaluating the toxicity of engineered nanomaterials (ENMS) it is important to use multiple bioassays based on different mechanisms of action. In this regard we evaluated the use of gene expression and common cytotoxicity measurements using as test materials, two selected nanoparticles with known differences in toxicity, 5 nm mercaptoundecanoic acid (MUA)-capped InP and CdSe quantum dots (QDs). We tested the effects of these QDs at concentrations ranging from 0.5 to 160 µg/mL on cultured normal human bronchial epithelial (NHBE) cells using four common cytotoxicity assays: the dichlorofluorescein assay for reactive oxygen species (ROS), the lactate dehydrogenase assay for membrane viability (LDH), the mitochondrial dehydrogenase assay for mitochondrial function, and the Comet assay for DNA strand breaks. RESULTS: The cytotoxicity assays showed similar trends when exposed to nanoparticles for 24 h at 80 µg/mL with a threefold increase in ROS with exposure to CdSe QDs compared to an insignificant change in ROS levels after exposure to InP QDs, a twofold increase in the LDH necrosis assay in NHBE cells with exposure to CdSe QDs compared to a 50% decrease for InP QDs, a 60% decrease in the mitochondrial function assay upon exposure to CdSe QDs compared to a minimal increase in the case of InP and significant DNA strand breaks after exposure to CdSe QDs compared to no significant DNA strand breaks with InP. High-throughput quantitative real-time polymerase chain reaction (qRT-PCR) data for cells exposed for 6 h at a concentration of 80 µg/mL were consistent with the cytotoxicity assays showing major differences in DNA damage, DNA repair and mitochondrial function gene regulatory responses to the CdSe and InP QDs. The BRCA2, CYP1A1, CYP1B1, CDK1, SFN and VEGFA genes were observed to be upregulated specifically from increased CdSe exposure and suggests their possible utility as biomarkers for toxicity. CONCLUSIONS: This study can serve as a model for comparing traditional cytotoxicity assays and gene expression measurements and to determine candidate biomarkers for assessing the biocompatibility of ENMs.1R01GM84702-01 - National Institute of General Medical Science

Does stakeholder pressure influence corporate GHG emissions reporting? Empirical evidence from Europe

Purpose – The purpose of this paper is to seek to shed light on the practice of incomplete corporate disclosure of quantitative Greenhouse gas (GHG) emissions and investigates whether external stakeholder pressure influences the existence, and separately, the completeness of voluntary GHG emissions disclosures by 431 European companies. Design/methodology/approach – A classification of reporting completeness is developed with respect to the scope, type and reporting boundary of GHG emissions based on the guidelines of the GHG Protocol, Global Reporting Initiative and the Carbon Disclosure Project. Logistic regression analysis is applied to examine whether proxies for exposure to climate change concerns from different stakeholder groups influence the existence and/or completeness of quantitative GHG emissions disclosure. Findings – From 2005 to 2009, on average only 15 percent of companies that disclose GHG emissions report them in a manner that the authors consider complete. Results of regression analyses suggest that external stakeholder pressure is a determinant of the existence but not the completeness of emissions disclosure. Findings are consistent with stakeholder theory arguments that companies respond to external stakeholder pressure to report GHG emissions, but also with legitimacy theory claims that firms can use carbon disclosure, in this case the incomplete reporting of emissions, as a symbolic act to address legitimacy exposures. Practical implications – Bringing corporate GHG emissions disclosure in line with recommended guidelines will require either more direct stakeholder pressure or, perhaps, a mandated disclosure regime. In the meantime, users of the data will need to carefully consider the relevance of the reported data and develop the necessary competencies to detect and control for its incompleteness. A more troubling concern is that stakeholders may instead grow to accept less than complete disclosure. Originality/value – The paper represents the first large-scale empirical study into the completeness of companies’ disclosure of quantitative GHG emissions and is the first to analyze these disclosures in the context of stakeholder pressure and its relation to legitimation

Climate change and asset prices: are corporate carbon disclosure and performance priced appropriately?

This paper empirically assesses the value relevance of information on corporate climate change disclosure and performance to asset prices, and discusses whether this information is priced appropriately. Findings indicate that corporate disclosures of quantitative GHG emissions and, to a lesser extent, carbon performance are value relevant. We use hand-collected information on quantitative greenhouse gas (GHG) emissions for 433 European companies and build portfolios based on GHG disclosure and performance. We regress portfolios on Carhart (1997) four factor models extended for industry effects over the years 2005 to 2009. Results show that investors achieved abnormal risk-adjusted returns of up to 13.05% annually by exploiting inefficiently priced positive effects of (complete) GHG emissions disclosure and good corporate climate change performance in terms of GHG efficiency. Results imply that, firstly, information costs involved in carbon disclosure and management do not present a burden on corporate financial resources. Secondly, investors should not neglect carbon disclosure and performance when making investment decisions. Thirdly, during the period analysed financial markets were inefficient in pricing publicly available information on carbon disclosure and performance. Mandatory and standardised information on carbon performance would consequently not only increase market efficiency but result in better allocation of capital within the real economy

How and when do big data investments pay off? The role of marketing affordances and service innovation

Big data technologies and analytics enable new digital services and are often associated with superior performance. However, firms investing in big data often fail to attain those advantages. To answer the questions of how and when big data pay off, marketing scholars need new theoretical approaches and empirical tools that account for the digitized world. Building on affordance theory, the authors develop a novel, conceptually rigorous, and practice-oriented framework of the impact of big data investments on service innovation and performance. Affordances represent action possibilities, namely what individuals or organizations with certain goals and capabilities can do with a technology. The authors conceptualize and operationalize three important big data marketing affordances: customer behavior pattern spotting, real-time market responsiveness, and data-driven market ambidexterity. The empirical analysis establishes construct validity and offers a preliminary nomological test of direct, indirect, and conditional effects of big data marketing affordances on perceived big data performance

Impact of short-chain galactooligosaccharides on the gut microbiome of lactose-intolerant individuals

Approximately 75% of the global human population are lactose malabsorbers. In a previous clinical trial, it was shown that feeding a high-purity galactooligosaccharide (>95% GOS) could improve symptoms of lactose-intolerant subjects, attaining lactose tolerance in a majority of subjects. To investigate the mechanism, we examined the microbiome of human subjects before and after GOS feeding. The results show a significant shift in the microbiome of responsive individuals, including lactose-fermenting microbes in their stools. The high-purity prebiotic GOS resulted in adaptive shifts in the microbiome and correlated with improvement in clinical symptoms

Sudden Cardiac Death Among Firefighters ≤45 Years of Age in the United States

Sudden cardiac death (SCD) is the leading cause of death in firefighters. Although on-duty SCD usually occurs in older victims almost exclusively because of coronary heart disease, no studies have examined causation across the career span. In the present retrospective case-control study, cases of SCD in young (aged ≤45 years) firefighters from the National Institute for Occupational Safety and Health fatality investigations (n = 87) were compared with 2 age- and gender-matched control groups: occupationally active firefighters (n = 915) and noncardiac traumatic firefighter fatalities (n = 56). Of the SCD cases, 63% were obese and 67% had a coronary heart disease-related cause of death. The SCD victims had much heavier hearts (522 ± 102 g) than noncardiac fatality controls (400 ± 91 g, p 450 g) was found in 66% of the SCD victims and conveyed a fivefold increase (95% confidence interval [CI] 1.93 to 12.4) in SCD risk. Furthermore, hypertension, including cases with left ventricular hypertrophy, increased SCD risk by 12-fold (95% CI 6.23 to 22.3) after multivariate adjustment. A history of cardiovascular disease and smoking were also independently associated with elevated SCD risk (odds ratio 6.89, 95% CI 2.87 to 16.5; and odds ratio 3.53, 95% CI 1.87 to 6.65, respectively). In conclusion, SCD in young firefighters is primarily related to preventable lifestyle factors. Obesity entry standards, smoking bans, and improved screening and/or wellness program are potential strategies to reduce SCD in younger firefighters

An open‑source low‑cost sensor for SNR‑based GNSS reflectometry : design and long‑term validation towards sea‑level altimetry

Monitoring sea level is critical due to climate change observed over the years. Global Navigation Satellite System Reflectometry (GNSS-R) has been widely demonstrated for coastal sea-level monitoring. The use of signal-to-noise ratio (SNR) observations from ground-based stations has been especially productive for altimetry applications. SNR records an interference pattern whose oscillation frequency allows retrieving the unknown reflector height. Here we report the development and validation of a complete hardware and software system for SNR-based GNSS-R. We make it available as open source based on the Arduino platform. It costs about US$200 (including solar power supply) and requires minimal assembly of commercial off-the-shelf components. As an initial validation towards applications in coastal regions, we have evaluated the system over approximately 1 year by the Guaíba Lake in Brazil. We have compared water-level altimetry retrievals with independent measurements from a co-located radar tide gauge (within 10 m). The GNSS-R device ran practically uninterruptedly, while the reference radar gauge suffered two malfunctioning periods, resulting in gaps lasting for 44 and 38 days. The stability of GNSS-R altimetry results enabled the detection of miscalibration steps (10 cm and 15 cm) inadvertently introduced in the radar gauge after it underwent maintenance. Excluding the radar gaps and its malfunctioning periods (reducing the time series duration from 317 to 147 days), we have found a correlation of 0.989 and RMSE of 2.9 cm in daily means. To foster open science and lower the barriers for entry in SNR-based GNSS-R research and applications, we make a complete bill of materials and build tutorials freely available on the Internet so that interested researchers can replicate the system

Benefits of adding fluticasone propionate/salmeterol to tiotropium in moderate to severe COPD

SummaryBackgroundCombining maintenance medications with different mechanisms of action may improve outcomes in COPD. In this study we evaluated the efficacy and safety of fluticasone/salmeterol (FSC) (250/50 mcg twice daily) when added to tiotropium (18 mcg once daily) (TIO) in subjects with symptomatic moderate to severe COPD.MethodsThis was a 24-week, randomized, double-blind, parallel group, multi-center study. Subjects 40 years or older with cigarette smoking history ≥10 pack-years and with the diagnosis of COPD and post-bronchodilator FEV1 ≥40 to ≤ 80% of predicted normal and FEV1/FVC of ≤0.70 were enrolled. Following a 4-week treatment with open-label TIO 18 mcg once daily, subjects were randomized in a double-blind fashion to either the addition of FSC 250/50 DISKUS twice daily or matching placebo. The primary efficacy endpoint was AM pre-dose FEV1 and secondary endpoints included other measures of lung function, rescue albuterol use, health status and exacerbations.ResultsThe addition of FSC to TIO significantly improved lung function indices including AM pre-dose FEV1, 2 h post-dose FEV1, AM pre-dose FVC, 2 h post-dose FVC and AM pre-dose IC compared with TIO alone. Furthermore, this combination was superior to TIO alone in reducing rescue albuterol use. However, there were no significant differences between the treatment groups in health status or COPD exacerbations. The incidence of adverse events was similar in both groups.ConclusionsThe addition of FSC to subjects with COPD treated with TIO significantly improves lung function without increasing the risk of adverse events. NCT00784550

Transgenic models of skin diseases

Background: Transgenic animals have greatly enhanced our understanding of the contribution of various structural and regulatory components to epidermal biology. The expression of mutant versions of these components in the epidermis of transgenic mice has generated animal models of specific human skin diseases

Infant Feeding Practices and Subsequent Dietary Patterns of School-Aged Children in a US Birth Cohort

BACKGROUND: Infant feeding practices are thought to shape food acceptance and preferences. However, few studies have evaluated whether these affect child diet later in life. OBJECTIVE: The study objective was to examine the association between infant feeding practices and dietary patterns (DPs) in school-aged children. DESIGN: A secondary analysis of data from a diverse prospective birth cohort with 10 years of follow-up (WHEALS [Wayne County Health Environment Allergy and Asthma Longitudinal Study]) was conducted. PARTICIPANTS/SETTING: Children from the WHEALS (Detroit, MI, born 2003 through 2007) who completed a food screener at age 10 years were included (471 of 1,258 original participants). MAIN OUTCOME MEASURES: The main outcome was DPs at age 10 years, identified using the Block Kids Food Screener. STATISTICAL ANALYSIS PERFORMED: Latent class analysis was applied for DP identification. Breastfeeding and age at solid food introduction were associated with DPs using a 3-step approach for latent class modeling based on multinomial logistic regression models. RESULTS: The following childhood DPs were identified: processed/energy-dense food (35%), variety plus high intake (41%), and healthy (24%). After weighting for loss to follow-up and covariate adjustment, compared with formula-fed children at 1 month, breastfed children had 0.41 times lower odds of the processed/energy-dense food DP vs the healthy DP (95% CI 0.14 to 1.25) and 0.53 times lower odds of the variety plus high intake DP (95% CI 0.17 to 1.61), neither of which were statistically significant. Results were similar, but more imprecise, for breastfeeding at 6 months. In addition, the association between age at solid food introduction and DP was nonsignificant, with each 1-month increase in age at solid food introduction associated with 0.81 times lower odds of the processed/energy-dense food DP relative to the healthy DP (95% CI 0.64 to 1.02). CONCLUSIONS: A significant association between early life feeding practices and dietary patterns at school age was not detected. Large studies with follow-up beyond early childhood that can also adjust for the multitude of potential confounders associated with breastfeeding are needed