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Jean Bourbeau,1 Mona Bafadhel,2 Neil C Barnes,3,4 Chris Compton,3 Valentina Di Boscio,3 David A Lipson,5,6 Paul W Jones,3,7 Neil Martin,3,8 Gudrun Weiss,3 David MG Halpin9 1Respiratory Epidemiology and Clinical Research Unit, Department of Medicine, McGill University and Research Institute of the McGill University Health Centre, Montreal, QC, Canada; 2Nuffield Department of Medicine, University of Oxford, Oxford, Oxfordshire, UK; 3Respiratory Therapy Area, GlaxoSmithKline, Brentford, Middlesex, UK; 4William Harvey Institute, Bart’s and the London School of Medicine and Dentistry, London, UK; 5Clinical Sciences, GlaxoSmithKline, Collegeville, PA, USA; 6Pulmonary, Allergy and Critical Care Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; 7Institute of Infection and Immunity, St George’s, University of London, London, UK; 8University of Leicester, Leicester, UK; 9University of Exeter Medical School, College of Medicine and Health, University of Exeter, Exeter, UKCorrespondence: Jean BourbeauMcGill University Health Centre (MUHC), 1001 Decarie Boulevard, Montreal, QC, H4A 3J1, CanadaTel +1 514 934-1934Fax +1 514 934-8577Email jean.bourbeau@mcgill.caAbstract: Chronic obstructive pulmonary disease (COPD) is associated with major healthcare and socioeconomic burdens. International consortia recommend a personalized approach to treatment and management that aims to reduce both symptom burden and the risk of exacerbations. Recent clinical trials have investigated single-inhaler triple therapy (SITT) with a long-acting muscarinic antagonist (LAMA), long-acting β2-agonist (LABA), and inhaled corticosteroid (ICS) for patients with symptomatic COPD. Here, we review evidence from randomized controlled trials showing the benefits of SITT and weigh these against the reported risk of pneumonia with ICS use. We highlight the challenges associated with cross-trial comparisons of benefit/risk, discuss blood eosinophils as a marker of ICS responsiveness, and summarize current treatment recommendations and the position of SITT in the management of COPD, including potential advantages in terms of improving patient adherence. Evidence from trials of SITT versus dual therapies in symptomatic patients with moderate to very severe airflow limitation and increased risk of exacerbations shows benefits in lung function and patient-reported outcomes. Moreover, the key benefits reported with SITT are significant reductions in exacerbations and hospitalizations, with data also suggesting reduced all-cause mortality. These benefits outweigh the ICS-class effect of higher incidence of study-reported pneumonia compared with LAMA/LABA. Important differences in trial design, baseline population characteristics, such as exacerbation history, and assessment of outcomes, have significant implications for interpreting data from cross-trial comparisons. Current understanding interprets the blood eosinophil count as a continuum that can help predict response to ICS and has utility alongside other clinical factors to aid treatment decision-making. We conclude that treatment decisions in COPD should be guided by an approach that considers benefit versus risk, with early optimization of treatment essential for maximizing long-term benefits and patient outcomes.Keywords: all-cause mortality, exacerbations, hospitalizations, ICS, LABA, LAMA

Photocatalytic building surfaces can harness sunlight to reduce urban air pollution. The NOx abatement capacity of TiO2-coated granules used in roofing products was evaluated for commercial product development. A laboratory test chamber and ancillary setup were built following conditions prescribed by ISO Standard 22197-1. It was validated by exposing reference P25-coated aluminum plates to a 3 L min−1 air flow enriched in 1 ppm NO under UVA irradiation (360 nm, 11.5 W m−2). We characterized prototype granule-surfaced asphalt shingles and loose granules prepared with different TiO2 loadings and post-treatment formulations. Tests performed at surface temperatures of 25 and 60 °C showed that NOx abatement was more effective at the higher temperature. Preliminary tests explored the use of 1 ppm NO2 and of 1 ppm and 0.3 ppm NO/NO2 mixtures. Specimens were aged in a laboratory accelerated weathering apparatus, and by exposure to the outdoor environment over periods that included dry and rainy seasons. Laboratory aging led to higher NO removal and NO2 formation rates, and the same catalyst activation was observed after field exposure with frequent precipitation. However, exposure during the dry season reduced the performance. This inactivation was mitigated by cleaning the surface of field-exposed specimens. Doubling the TiO2 loading led to a 50–150% increase in NO removal and NOx deposition rates. Application of different post-treatment coatings decreased NO removal rates (21–35%) and NOx deposition rates (26–74%) with respect to untreated granules. The mass balance of nitrogenated species was assessed by extracting granules after UV exposure in a 1 ppm NO-enriched atmosphere.

The international GEOTRACES program has been instrumental in demonstrating how marine sediments are a critical source of dissolved Fe to the world's oceans. Here, we present dissolved iron (dFe) from the GEOTRACES North Pacific GP15 section, which, alongside other sediment‐source tracers (including dissolved δ56Fe, Mn, 228Ra, and particulate Fe), allows for identification of the dFe provenance of three distinct dFe depth maxima at the Alaskan margin. Two of these (shelf and abyssal depths) are of local Alaskan sedimentary origin. The third, a mid‐depth dFe maximum with an absence of 228Ra, is an advected signal that, based on tracer data from Western Pacific GEOTRACES transects and circulation models, must be advected from sedimentary sources on the Asian margin, ∼5,000 km away. This study illustrates the importance of measuring diagnostic sedimentary tracers like radium when assigning local margins as sedimentary sources of marine trace metal budgets. Plain Language Summary: Iron is an essential, yet limiting, micronutrient for marine primary producers, and thus influences patterns of global oceanic primary productivity and carbon exchange. In recent years, the International GEOTRACES program has highlighted that marine sediments, hydrothermal vents, and atmospheric dust all supply dissolved iron to the oceans. Here, we investigated the sources of dissolved iron to the Eastern North Pacific Ocean, using samples collected on the U.S. GEOTRACES GP15 Pacific Meridional Cruise that sailed from Alaska to Tahiti in 2018. We identified three elevated dissolved iron features close to the Alaskan continental margin, with two originating from local sedimentary sources (shelf and abyss). The third, an intermediate depth dissolved iron plume that extends south into the gyre, is not of local sedimentary origin, but instead results from long‐distance transport of dissolved iron from Asian marginal sediment sources. A critical aspect of this study is the use of multiple chemical tracers such as radium, iron, and manganese, coupled with ocean circulation models, to correctly attribute the sources of trace metals to the ocean. Key Points: Three distinct dFe maxima were identified close to the Alaskan margin at different depths. Two are of local origin (shelf and abyssal)An intermediate depth dFe plume with an absence of Mn and Ra, is a distal advected signal from Asian margin sedimentary sources (5,000 km away)A multiple tracer approach of Fe, Mn, and Ra was necessary to rule out what appeared to be a local margin source [ABSTRACT FROM AUTHOR]

To identify and characterize localized urban heat- and cool-island signals embedded within the temperature field of a large urban-climate archipelago, fine-resolution simulations with a modified urbanized version of the WRF meteorological model were carried out as basis for siting fixed weather monitors and designing mobile-observation transects. The goal was to characterize variations in urban heat during summer in Los Angeles, California. Air temperatures measured with a shielded sensor mounted atop an automobile in the summers of 2016 and 2017 were compared to model output and also correlated to surface physical properties focusing on neighborhood-scale albedo and vegetation canopy cover. The study modeled and measured the temperature response to variations in surface properties that already exist in the real world, i.e., realistic variations in albedo and canopy cover that are attainable through current building and urban design practices. The simulated along-transect temperature from a modified urbanized WRF model was compared to the along-transect observed temperature from 15 mobile traverses in one area near downtown Los Angeles and another in an inland basin (San Fernando Valley). The observed transect temperature was also correlated to surface physical properties characterizations that were developed for input to the model. Both comparisons were favorable, suggesting that (1) the model can reliably be used in siting fixed weather stations and designing mobile-transect routes to characterize urban heat and (2) that except for a few cases with opposite co-varying influences, the correlations between observed temperature and albedo and between observed temperature and canopy cover were each negative, ranging from -1.0 to -9.0 °C per 0.1 increase in albedo and from -0.1 to -2.2 °C per 0.1 increase in canopy cover. Observational data from the analysis domains pointed to a wind speed threshold of 3 m/s. Below this threshold the variations in air temperature could be explained by land use and surface properties within a 500-m radius of each observation point. Above the threshold, air temperature was influenced by the properties of the surface within a 1-km upwind fetch. Of relevance to policy recommendations, the study demonstrates the significant real-world cooling effects of increasing urban albedo and vegetation canopy cover. Based on correlations between the observed temperature (from mobile transects) and surface physical properties in the study domains, the analysis shows that neighborhood-scale (500-m) cooling of up to 2.8 °C during the daytime can be achieved by increasing albedo. A neighborhood can also be cooled by up to 2.3 °C during the day and up to 3.3 °C at night by increasing canopy cover. The analysis also demonstrates the suitability of using fine-resolution meteorological models to design mobile-transect routes or site-fixed weather monitors in order to quantify urban heat and the efficacy of albedo and canopy cover countermeasures. The results also show that the model is capable of accurately predicting the geographical locations and the magnitudes of localized urban heat and cool islands. Thus the model results can also be used to devise urban-heat mitigation measures.

Raising the albedo (solar reflectance) of streets can lower outside air temperature, reduce building energy use, and improve air quality in cities. However, the production and installation of pavement maintenance and rehabilitation treatments with enhanced albedo (“cool” pavements) may entail more or less energy consumption and carbon emission than that of less-reflective treatments. We developed several case studies in which a cool surface treatment is substituted for a more typical treatment (that is, a cool technology is selected instead of a more typical technology). We then assessed over a 50-year analysis period the changes in primary energy demand (PED, excluding feedstock energy) and global warming potential (GWP, meaning carbon dioxide equivalent) in Los Angeles and Fresno, California. The analysis considers two stages of the pavement life cycle: materials and construction (MAC), comprising material production, transport, and construction; and use, scoped as the influence of pavement albedo on cooling, heating, and lighting energy consumption in buildings. In Los Angeles, substituting a styrene acrylate reflective coating or a chip seal for a slurry seal in routine maintenance, or a bonded concrete overlay on asphalt (BCOA) without supplementary cementitious materials (SCM) for mill-and-fill asphalt concrete in conventional or long-life rehabilitation, induced MAC-stage PED and GWP penalties that substantially exceeded use-stage savings, primarily due to material production. Modified rehabilitation cases in which SCM comprised 21% to 50% of the BCOA's total cementitious content by mass (portland cement + SCM) yielded smaller total (MAC + use) PED and GWP penalties, or even total PED and GWP savings. Trends in Fresno were similar, with some differences in GWP outcomes that result from Fresno's longer heating season. The modified rehabilitation cases using BCOA with high SCM content yielded total GWP savings in each city; all other cases yielded total GWP penalties. The magnitude of the one-time GWP offset offered by global cooling from the increased albedo itself always, and sometimes greatly, exceeded the 50-year total GWP penalty or savings. In Los Angeles, the annual building conditioning (cooling + heating) PED and energy cost savings intensities yielded by cool pavements were each about an order of magnitude smaller than the corresponding savings from cool roofs.

Solar reflective “cool pavements” have been proposed as a potential heat mitigation strategy for cities. However, previous research has not systematically investigated the extent to which cool pavements could reduce urban temperatures. In this study we investigated the climate impacts of widespread deployment of cool pavements in California cities. Using the Weather Research and Forecasting model, we simulated the current climate of California at 4 km spatial resolution. Comparing this simulation to 105 weather stations in California suggested an overall mean bias (model minus observation) of -0.30°C. Widespread pavement albedo increases of 0.1 and 0.4 in California cities were then simulated. Comparing temperature reductions for each scenario showed that the climate response to pavement albedo modification was nearly linear. Temperature reductions at 14:00 local standard time were found to be 0.32°C per 0.1 increase in grid cell average albedo. Temperature reductions were found to peak in the late morning and evening when (a) boundary layer heights were low and (b) solar irradiance (late morning) and heat accumulation in the pavement (evening) was high. Temperature reductions in summer were found to exceed those in winter, as expected. After scaling the results using realistic data-derived urban canyon morphologies and an off-line urban canyon albedo model, annual average surface air temperature reductions from increasing pavement albedo by 0.4 ranged from 0.18°C (Palm Springs) to 0.86°C (San Jose). The variation among cities was due to differences in baseline climate, size of the city, urban fraction, and urban morphology.

The ability of a climate model to accurately simulate the urban cooling effect of raising street albedo may be hampered by unrealistic representations of street geometry in the urban canyon. Even if the climate model is coupled to an urban canyon model (UCM), it is hard to define detailed urban geometries in UCMs. In this study, we relate simulated surface air temperature change to canyon albedo change. Using this relationship, we calculate scaling factors to adjust previously obtained surface air temperature changes that were simulated using generic canyon geometries. The adjusted temperature changes are obtained using a proposed multi-reflection urban canyon albedo model (UCAM), avoiding the need to rerun computationally expensive climate models. The adjusted temperature changes represent those that would be obtained from simulating with city-specific (local) geometries. Local urban geometries are estimated from details of the city's building stock and the city's street design guidelines. As a case study, we calculated average citywide seasonal scaling factors for realistic canyon geometries in Sacramento, California based on street design guidelines and building stock. The average scaling factors are multipliers used to adjust air temperature changes previously simulated by a Weather Research and Forecasting model coupled to an urban canyon model in which streets extended from wall to wall (omitting setbacks, such as sidewalks and yards). Sacramento's scaling factors ranged from 2.70 (summer) to 3.89 (winter), demonstrating the need to consider the actual urban geometry in urban climate studies.

The climate warming effects of accelerated urbanization along with projected global climate change raise an urgent need for sustainable mitigation and adaptation strategies to cool urban climates. Our modeling results show that historical urbanization in the Los Angeles and San Diego metropolitan areas has increased daytime urban air temperature by 1.3 °C, in part due to a weakening of the onshore sea breeze circulation. We find that metropolis-wide adoption of cool roofs can meaningfully offset this daytime warming, reducing temperatures by 0.9 °C relative to a case without cool roofs. Residential cool roofs were responsible for 67% of the cooling. Nocturnal temperature increases of 3.1 °C from urbanization were larger than daytime warming, while nocturnal temperature reductions from cool roofs of 0.5 °C were weaker than corresponding daytime reductions. We further show that cool roof deployment could partially counter the local impacts of global climate change in the Los Angeles metropolitan area. Assuming a scenario in which there are dramatic decreases in greenhouse gas emissions in the 21st century (RCP2.6), mid- and end-of-century temperature increases from global change relative to current climate are similarly reduced by cool roofs from 1.4 °C to 0.6 °C. Assuming a scenario with continued emissions increases throughout the century (RCP8.5), mid-century warming is significantly reduced by cool roofs from 2.0 °C to 1.0 °C. The end-century warming, however, is significantly offset only in small localized areas containing mostly industrial/commercial buildings where cool roofs with the highest albedo are adopted. We conclude that metropolis-wide adoption of cool roofs can play an important role in mitigating the urban heat island effect, and offsetting near-term local warming from global climate change. Global-scale reductions in greenhouse gas emissions are the only way of avoiding long-term warming, however. We further suggest that both climate mitigation and adaptation can be pursued simultaneously using 'cool photovoltaics'.

As the least expensive category of high-slope roofing in the U.S., shingles are found on the roofs of about 80% of U.S. homes, and constitute about 80% (by product area) of this market. Shingles are also among the least reflective high-slope roofing products, with few cool options on the market. The widespread use of cool roofs in the two warmest U.S. climate zones could reduce annual residential cooling energy use in these zones by over 7%. This project targets the development of high-performance cool shingles with initial solar reflectance at least 0.40 and a cost premium not exceeding US$0.50/ft².Phase 1 of the current study explored three approaches to increasing shingle reflectance. Method A replaces dark bare granules by white bare granules to enhance the near-infrared reflectance attained with cool pigments. Method B applies a white basecoat and a cool-color topcoat to a shingle surfaced with dark bare granules. Method C applies a visually clear, NIR-reflecting surface treatment to a conventionally colored shingle. Method A was the most successful, but our investigation of Method B identified roller coating as a promising top-coating technique, and ourstudy of Method C developed a novel approach based on a nanowire mesh.Method A yielded red, green, brown, and black faux shingles with solar reflectance up to 0.39 with volumetric coloration. Since the base material is white, these reflectances can readily be increased by using less pigment. The expected cost premium for Method A shingles is less than our target limit of $0.50/ft², and would represent less than a 10% increase in the installed cost of a shingle roof. Using inexpensive but cool (spectrally selective) iron oxide pigments to volumetrically colorwhite limestone synthesized from sequestered carbon and seawater appears to offer high albedo at low cost.In Phase 2, we plan to refine the cool shingle prototypes, manufacture cool granules, and manufacture and market high-performance cool shingles.

During 2012–2014, drought in California resulted in policies to reduce water consumption. One measure pursued was replacing lawns with landscapes that minimize water consumption, such as drought-tolerant vegetation. If implemented at broad scale, this strategy would result in reductions in irrigation and changes in land surface characteristics. In this study, we employ a modified regional climate model to assess the climatic consequences of adopting drought-tolerant vegetation over the Los Angeles metropolitan area. Transforming lawns to drought-tolerant vegetation resulted in daytime warming of up to 1.9°C, largely due to decreases in irrigation that shifted surface energy partitioning toward higher sensible and lower latent heat flux. During nighttime, however, adopting drought-tolerant vegetation caused mean cooling of 3.2°C, due to changes in soil thermodynamic properties and heat exchange dynamics between the surface and subsurface. Our results show that nocturnal cooling effects, which are larger in magnitude and of great importance for public health during heat events, could counterbalance the daytime warming attributed to the studied water conservation strategy. A more aggressive implementation, assuming all urban vegetation was replaced with drought-tolerant vegetation, resulted in an average daytime cooling of 0.2°C, largely due to strengthened sea breeze patterns, highlighting the important role of land surface roughness in this coastal megacity.

Twenty-nine chemotherapy-naive patients with primary hepatocellular carcinoma were treated with oral beta-all trans-retinoic acid (retinoic acid, TRA 50 mg/m2 t.i.d.) on a 3-week on/one week off schedule until progression or grade 3 or 4 toxicity. Eligibility requirements allowed abnormal liver function tests as long as the creatinine and bilirubin levels were normal. No responses were seen and the median survival was four months. Grade 3 side effects occurred in II patients and grade 4 in four and included a wide range of toxicities. The results indicate that oral TRA is ineffective against primary hepatocellular carcinoma and suggest that dose-modification of this retinoid may be required in patients with significant malignant hepatic involvement.