The Hepatotoxicity and Urinary Metabolites of 2,4- And 2,6-Dimethylaniline in the Rat and Dog (Aromatic Amines).

This study was designed to investigate the hepatotoxicity and urinary metabolites of 2,4- and 2,6-DMA in the dog and rat and the covalent binding of the two isomers in the rat as differences in metabolism may be related to the divergent hepatic responses. Male Beagles were orally dosed for 1 or 10 days with 2,6- or 2,4-DMA at 25 mg/kg. Male Fischer 344 rats were gavaged with 2,6- or 2,4-DMA at 25% of their respective LD50\u27s (262.5 mg/kg; 117/mg/kg) for the same time period. The effects of phenobarbital (PB), 3-methylcholanthrene (3MC) and SKF-525A on the hepatotoxicity and metabolites of 2,4- and 2,6-DMA were also investigated. 24 Hr. urine samples were analysed by GC and GC/MS; liver sections were evaluated by light and electron microscopy. A final group of rats received (\u2714)C-2,4- or -2,6-DMA after a 9 day pretreatment with nonlabelled compounds. 2,6-DMA induced hepatic fatty degeneration in all treated dogs; 2,4-DMA caused no detectable lesions. In rats 2,6-DMA produced no significant liver lesions, whereas 2,4-DMA induced hepatomegaly and a subtle but distinct change characterized by swollen cells with voluminous homogeneous cytoplasm and segregation or clumping of cytoplasmic substructures. Concurrent treatment with PB and 2,4-DMA resulted in death of 50% of the animals by Day 5. 3MC treatment enhanced the 2,4-DMA lesion. 2,4-DMA alleviated an SKF-525A - induced midzonal fatty degeneration of the liver, whereas 2,6-DMA was less effective in this regard. The major urinary metabolite of 2,4-DMA in the dog was 6-hydroxy-2,4-DMA. Minor metabolites included 4-amino-3-methyl-benzoic acid and N,2,4-trimethylaniline. The major urinary metabolite of 2,6-DMA was 4-hydroxy-2,6-DMA. Minor metabolites included 2-amino-3-methyl-benzoic acid, N,2,6-trimethylaniline, 2,6-dimethylnitrosobenzene, 4-imino-3,5-dimethyl-quinone, and the glycine conjugate of the benzoic acid. Rats produced N-acetyl-4-amino-3-methyl-benzoic acid as the major metabolite of 2,4-DMA and N,2,4-trimethylaniline in small amounts. 2,6-DMA was primarily excreted as 4-hydroxy-2,6-DMA; N,2,6-trimethylaniline was a minor metabolite. The covalent binding of (\u2714)C-2,4-DMA to rat hepatic DNA, RNA or protein was significantly greater than that of (\u2714)C-2,6-DMA. The above results appear to indicate that differences in metabolism, with possible activation to reactive metabolite(s), are important in the divergent hepatic effects of 2,4- and 2,6-DMA in the rat and dog. (Abstract shortened with permission of author.)

Do Products Labeled Retailer “Exclusive” Affect Consumer Behavior?

Many large retailers offer “advertised as retailer exclusive products” or AREPs. Retailers work with manufacturers to produce these unique, retailer exclusive versions of otherwise common products. While not all retailer exclusive products are advertised as “exclusive,” AREPs are advertised and labeled as retailer exclusives. The retailer exclusive product attributes are often “trivial,” but still may add customer value and discourage price comparison shopping. Here, two experiments assess AREPs effects on consumers. Contrary to managerial expectations, the findings suggest that AREP exclusivity promotions are ineffective at influencing consumers, but that the choice of exclusive, seemingly “trivial” attribute can sometimes be a significant negative influence on consumers. Further, the authors suggest contexts that may encourage specific responses to retailer exclusive product promotions and trivial attributes

Systems thinking and efficiency under emissions constraints: Addressing rebound effects in digital innovation and policy

Innovations and efficiencies in digital technology have lately been depicted as paramount in the green transition to enable the reduction of greenhouse gas emissions, both in the information and communication technology (ICT) sector and the wider economy. This, however, fails to adequately account for rebound effects that can offset emission savings and, in the worst case, increase emissions. In this perspective, we draw on a transdisciplinary workshop with 19 experts from carbon accounting, digital sustainability research, ethics, sociology, public policy, and sustainable business to expose the challenges of addressing rebound effects in digital innovation processes and associated policy. We utilize a responsible innovation approach to uncover potential ways forward for incorporating rebound effects in these domains, concluding that addressing ICT-related rebound effects ultimately requires a shift from an ICT efficiency-centered perspective to a “systems thinking” model, which aims to understand efficiency as one solution among others that requires constraints on emissions for ICT environmental savings to be realized

Contributions of mean and shape of blood pressure distribution to worldwide trends and variations in raised blood pressure: A pooled analysis of 1018 population-based measurement studies with 88.6 million participants

© The Author(s) 2018. Background: Change in the prevalence of raised blood pressure could be due to both shifts in the entire distribution of blood pressure (representing the combined effects of public health interventions and secular trends) and changes in its high-blood-pressure tail (representing successful clinical interventions to control blood pressure in the hypertensive population). Our aim was to quantify the contributions of these two phenomena to the worldwide trends in the prevalence of raised blood pressure. Methods: We pooled 1018 population-based studies with blood pressure measurements on 88.6 million participants from 1985 to 2016. We first calculated mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP) and prevalence of raised blood pressure by sex and 10-year age group from 20-29 years to 70-79 years in each study, taking into account complex survey design and survey sample weights, where relevant. We used a linear mixed effect model to quantify the association between (probittransformed) prevalence of raised blood pressure and age-group- and sex-specific mean blood pressure. We calculated the contributions of change in mean SBP and DBP, and of change in the prevalence-mean association, to the change in prevalence of raised blood pressure. Results: In 2005-16, at the same level of population mean SBP and DBP, men and women in South Asia and in Central Asia, the Middle East and North Africa would have the highest prevalence of raised blood pressure, and men and women in the highincome Asia Pacific and high-income Western regions would have the lowest. In most region-sex-age groups where the prevalence of raised blood pressure declined, one half or more of the decline was due to the decline in mean blood pressure. Where prevalence of raised blood pressure has increased, the change was entirely driven by increasing mean blood pressure, offset partly by the change in the prevalence-mean association. Conclusions: Change in mean blood pressure is the main driver of the worldwide change in the prevalence of raised blood pressure, but change in the high-blood-pressure tail of the distribution has also contributed to the change in prevalence, especially in older age groups

Rising rural body-mass index is the main driver of the global obesity epidemic in adults

Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities(.)(1,2) This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity(3-6). Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.Peer reviewe

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure