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The latest information from Hiroshima and Nagasaki on radiation-induced cancer in man includes new DS86 dose assignments and extension of the Life-Span Study Sample cohort through 1985. The implications of these new doses and updated data for the assessment of cancer risk at low to moderate doses have been evaluated. Results from the fitting of three dose-response models (linear, quadratic, linear-quadratic) to the data at doses less than 1.5 Gy are reported. Based on statistical analyses of the authors' results, comments are made concerning the possible shapes of dose-response curves for human cancer.

The operation of a building connects the building, its performance and its end-users. When a mismatch occurs between users' expectations and operations processes, then complaints can arise. The use of enhanced complaint handling processes is investigated to ascertain whether this can help diagnose performance problems. Two LEED Platinum-rated office buildings form the basis for a case study of the components that make up an enhanced complaint handling process. Some of the social dynamics of complaints in buildings are consequently discussed. It is found that an enhanced complaint handling approach could contribute to a form of ongoing commissioning that goes beyond primarily reactive or dismissive treatments of complaints. Le fonctionnement d'un immeuble etablit des rapports entre l'immeuble, ses performances et ses utilisateurs finaux. Lorsqu'un decalage se produit entre les attentes des utilisateurs et les processus d'exploitation, des plaintes peuvent alors s'elever. L'utilisation de processus ameliore...

We assessed the physical, chemical and toxicological characteristics of particulate emissions from four light-duty gasoline direct injection vehicles when operated over the LA92 driving cycle. Our results showed that particle mass and number emissions increased markedly during accelerations. For three of the four vehicles tested, particulate matter (PM) mass and particle number emissions were markedly higher during cold-start and the first few accelerations following the cold-start period than during the hot running and hot-start segments of the LA92 cycle. For one vehicle (which had the highest emissions overall) the hot-start and cold-start PM emissions were similar. Black carbon emissions were also much higher during the cold-start conditions, indicating severe fuel wetting leading to slow evaporation and pool burning, and subsequent soot formation. Particle number concentrations and black carbon emissions showed large reductions during the urban and hot-start phases of the test cycle. The oxidative potential of PM was quantified with both a chemical and a biological assay, and the gene expression impacts of the PM in a macrophage model with PCR (polymerase chain reaction) and ELISA (enzyme-linked immunosorbent assay) analyses. Inter- and intra-vehicle variability in oxidative potential per milligram of PM emitted was relatively low for both oxidative assays, suggesting that real-world emissions and exposure can be estimated with distance-normalized emission factors. The PCR response from signaling markers for oxidative stress (e.g., NOX1) was greater than from inflammatory, AhR (aryl hydrocarbon receptor), or MAPK (mitogen-activated protein kinase) signaling. Protein production associated with inflammation (tumor necrosis factor alpha-TNFα) and oxidative stress (HMOX-1) were quantified and displayed relatively high inter-vehicle variability, suggesting that these pathways may be activated by different PM components. Correlation of trace metal concentrations and oxidative potential suggests a role for small, insoluble particles in inducing oxidative stress.

Humans are exposed to complex mixtures of phthalates. Gestational exposure to phthalates has been linked to preeclampsia and preterm birth through potential pathways such as endocrine disruption, oxidative stress, and inflammation. Eicosanoids are bioactive signaling lipids that are related to a variety of homeostatic and inflammatory processes. We investigated associations between urinary phthalates and their mixtures with plasma eicosanoid levels during pregnancy using the PROTECT cohort in Puerto Rico (N = 655). After adjusting for covariates, we estimated pair-wise associations between the geometric mean of individual phthalate metabolite concentrations across pregnancy and eicosanoid biomarkers using multivariable linear regression. We used bootstrapping of adaptive elastic net regression (adENET) to evaluate phthalate mixtures associated with eicosanoids and subsequently create environmental risk scores (ERS) to represent weighted sums of phthalate exposure for each individual. After adjusting for false-discovery, in single-pollutant analysis, 14 of 20 phthalate metabolites or parent compound indices showed significant and primarily negative associations with multiple eicosanoids. In our mixture analysis, associations with several metabolites of low molecular weight phthalates - DEP, DBP, and DIBP - became prominent. Additionally, MEHHTP and MECPTP, metabolites of a new phthalate replacement, DEHTP, were selected as important predictors for determining the concentrations of multiple eicosanoids from different pathway groups. A unit increase in phthalate ERS derived from bootstrapping of adENET was positively associated with several eicosanoids mainly from Cytochrome P450 pathway. For example, an increase in ERS was associated with 11(S)-HETE (β = 1.6, 95% CI: 0.020, 3.180), (±)11,12-DHET (β = 2.045, 95% CI: 0.250, 3.840), 20(S)-HETE (β = 0.813, 95% CI: 0.147, 1.479), and 9 s-HODE (β = 2.381, 95% CI: 0.657, 4.104). Gestational exposure to phthalates and phthalate mixtures were associated with eicosanoid levels during pregnancy. Results from the mixture analyses underscore the complexity of physiological impacts of phthalate exposure and call for further in-depth studies to examine these relationships.

Aromatic hydrocarbons (AHs) are both hazardous air pollutants and important precursors to ozone and secondary organic aerosols. Here we investigated 14 C6-C9 AHs at one urban, one suburban and two rural sites in the Pearl River Delta region during November-December 2009. The ratios of individual aromatics to acetylene were compared among these contrasting sites to indicate their difference in source contributions from solvent use and vehicle emissions. Ratios of toluene to benzene (T/B) in urban (1.8) and suburban (1.6) were near that of vehicle emissions. Higher T/B of 2.5 at the rural site downwind the industry zones reflected substantial contribution of solvent use while T/B of 0.8 at the upwind rural site reflected the impact of biomass burning. Source apportionment by positive matrix factorization (PMF) revealed that solvent use, vehicle exhaust and biomass burning altogether accounted for 89-94% of observed AHs. Vehicle exhaust was the major source for benzene with a share of 43-70% and biomass burning in particular contributed 30% to benzene in the upwind rural site; toluene, C8-aromatics and C9-aromatics, however, were mainly from solvent use, with contribution percentages of 47-59%, 52-59% and 41-64%, respectively.

Naltrexone, a compound with high affinity for the mu opioid receptor (MOP-R) reduces alcohol consumption. SoRI-9409 is a derivative of naltrexone that has highest affinity at delta opioid receptors (DOP-Rs). We have investigated the effects of SoRI-9409 on ethanol consumption to determine the consequences of altering the naltrexone compound to a form with increased efficacy at DOP-Rs.Effects of the opioid receptor antagonists, SoRI-9409 (0-30 mg/kg, IP), naltrexone (0-30 mg/kg, IP), or naltrindole (0-10 mg/kg, IP) on ethanol consumption was measured in high- and low-ethanol-consuming rats with two different drinking paradigms. SoRI-9409-, naltrexone-, and naltrindole-mediated inhibition of DOP-R-stimulated [(35)S]GTP gamma S binding was measured in brain membranes prepared from high-ethanol-consuming rats. The effects of SoRI-9409 on morphine-mediated analgesia, conditioned place preference, and anxiety were also examined.In high- but not low-ethanol-consuming animals, SoRI-9409 is threefold more effective and selective at reducing ethanol consumption when compared with naltrexone or naltrindole for up to 24 hours. SoRI-9409 administered daily for 28 days continuously reduced ethanol consumption, and when the administration of SoRI-9409 was terminated, the amount of ethanol consumed remained lower compared with vehicle-treated animals. Furthermore, SoRI-9409 inhibits DOP-R-stimulated [(35)S]GTP gamma S binding in brain membranes of high-ethanol-consuming rats.SoRI-9409 causes selective and long-lasting reductions of ethanol consumption. This suggests that compounds that have high affinity for DOP-Rs such as SoRI-9409 might be promising candidates for development as a novel therapeutic for the treatment of alcoholism.

Net anthropogenic emissions of carbon dioxide (CO2) must approach zero by mid-century (2050) in order to stabilize the global mean temperature at the level targeted by international efforts1-5. Yet continued expansion of fossil-fuel-burning energy infrastructure implies already 'committed' future CO2 emissions6-13. Here we use detailed datasets of existing fossil-fuel energy infrastructure in 2018 to estimate regional and sectoral patterns of committed CO2 emissions, the sensitivity of such emissions to assumed operating lifetimes and schedules, and the economic value of the associated infrastructure. We estimate that, if operated as historically, existing infrastructure will cumulatively emit about 658 gigatonnes of CO2 (with a range of 226 to 1,479 gigatonnes CO2, depending on the lifetimes and utilization rates assumed). More than half of these emissions are predicted to come from the electricity sector; infrastructure in China, the USA and the 28 member states of the European Union represents approximately 41 per cent, 9 per cent and 7 per cent of the total, respectively. If built, proposed power plants (planned, permitted or under construction) would emit roughly an extra 188 (range 37-427) gigatonnes CO2. Committed emissions from existing and proposed energy infrastructure (about 846 gigatonnes CO2) thus represent more than the entire carbon budget that remains if mean warming is to be limited to 1.5 degrees Celsius (°C) with a probability of 66 to 50 per cent (420-580 gigatonnes CO2)5, and perhaps two-thirds of the remaining carbon budget if mean warming is to be limited to less than 2 °C (1,170-1,500 gigatonnes CO2)5. The remaining carbon budget estimates are varied and nuanced14,15, and depend on the climate target and the availability of large-scale negative emissions16. Nevertheless, our estimates suggest that little or no new CO2-emitting infrastructure can be commissioned, and that existing infrastructure may need to be retired early (or be retrofitted with carbon capture and storage technology) in order to meet the Paris Agreement climate goals17. Given the asset value per tonne of committed emissions, we suggest that the most cost-effective premature infrastructure retirements will be in the electricity and industry sectors, if non-emitting alternatives are available and affordable4,18.