This bottom‐up modeling study, supported by new population census 2011 data, simulates ozone (O3) and fine particulate matter (PM2.5) exposure on local to regional scales. It quantifies, present‐day ...premature mortalities associated with the exposure to near‐surface PM2.5 and O3 concentrations in India using a regional chemistry model. We estimate that PM2.5 exposure leads to about 570,000 (CI95: 320,000–730,000) premature mortalities in 2011. On a national scale, our estimate of mortality by chronic obstructive pulmonary disease (COPD) due to O3 exposure is about 12,000 people. The Indo‐Gangetic region accounts for a large part (~42%) of the estimated mortalities. The associated lost life expectancy is calculated as 3.4 ± 1.1 years for all of India with highest values found for Delhi (6.3 ± 2.2 years). The economic cost of estimated premature mortalities associated with PM2.5 and O3 exposure is about 640 (350–800) billion USD in 2011, which is a factor of 10 higher than total expenditure on health by public and private expenditure.
Key Points
PM2.5 exposure is causing 570,000 premature mortalities
Economic cost of estimated premature mortalities is about 640 billion USD
PM2.5 should be the primary target for reducing pollution impacts on health
The impact of a typical pre-monsoon season (April–June) dust storm event on the regional aerosol optical properties and radiation budget in northern India is analyzed. The dust storm event lasted ...from 17 to 22 April 2010 and the Weather Research and Forecasting model coupled with Chemistry (WRF-Chem) estimated total dust emissions of 7.5 Tg over the model domain. Both in situ (AERONET – Aerosol Robotic Network) and satellite observations show significant increase (> 50%) in local to regional scale aerosol optical depth (AOD) and decrease (> 70%) in the Ångström exponent (α) during this period. Amongst the AERONET sites in this region, Kanpur was influenced the most, where the AOD reached up to 2.1 and the α decreased to −0.09 during the dust storm period. The WRF-Chem model reproduced the spatial and temporal distributions of dust plumes and aerosol optical properties but generally underestimated the AOD. The average MODIS and WRF-Chem AOD (550 nm) values in a subregion (70–80° E, 25–30° N) affected the most by the dust storm are estimated as 0.80 ± 0.30 and 0.68 ± 0.28, respectively. Model results show that dust particles cool the surface and the top of the atmosphere, but warm the atmosphere itself. The radiative perturbation due to dust aerosols averaged over the subregion is estimated as −2.9 ± 3.1 W m−2 at the top of the atmosphere, 5.1 ± 3.3 W m−2 in the atmosphere and −8.0 ± 3.3 W m−2 at the surface. The simulated instantaneous cooling under the dust plume was much higher and reached −227 and −70 W m−2 at the surface and the top of the atmosphere, respectively. The impact of these radiative perturbations on the surface energy budget is estimated to be small on a regional scale but significant locally.
Summary Adenoid cystic carcinomas (ACC) are rare cancers usually arising in the salivary glands. Once metastatic, the natural history can vary; some patients with indolent cancer remain asymptomatic ...for long periods, whereas others have rapidly progressive disease. Chemotherapy is generally reserved for the palliative treatment of symptomatic locally recurrent or metastatic disease that is not amenable to further surgery or radiation. Prospective trials of chemotherapy in advanced ACC are limited, and the optimum regimen is unclear. The aim of this systematic review is to summarise and rate the quality of trials assessing chemotherapy for treatment of ACC, by use of the European Lung Cancer Working Party scoring system. Endpoints evaluated include tumour response and rates of symptomatic improvement. 34 trials involving 441 patients are included. We give evidence-based recommendations for management of ACC with chemotherapy, along with considerations for the design of future clinical trials in this disease.
Purpose There are no approved treatments for recurrent/metastatic head and neck squamous cell carcinoma refractory to platinum and cetuximab. In the single-arm, phase II KEYNOTE-055 study, we ...evaluated pembrolizumab, an anti-programmed death 1 receptor antibody, in this platinum- and cetuximab-pretreated population with poor prognosis. Methods Eligibility stipulated disease progression within 6 months of platinum and cetuximab treatment. Patients received pembrolizumab 200 mg every 3 weeks. Imaging was performed every 6 to 9 weeks. Primary end points: overall response rate (Response Evaluation Criteria in Solid Tumors v1.1, central review) and safety. Efficacy was assessed in all dosed patients and in subgroups on the basis of programmed death ligand 1 (PD-L1) expression and human papillomavirus (HPV) status. Results Among 171 patients treated, 75% received two or more prior lines of therapy for metastatic disease, 82% were PD-L1 positive, and 22% were HPV positive. At the time of analysis, 109 patients (64%) experienced a treatment-related adverse event; 26 patients (15%) experienced a grade ≥ 3 event. Seven patients (4%) discontinued treatment, and one died of treatment-related adverse events. Overall response rate was 16% (95% CI, 11% to 23%), with a median duration of response of 8 months (range, 2+ to 12+ months); 75% of responses were ongoing at the time of analysis. Response rates were similar in all HPV and PD-L1 subgroups. Median progression-free survival was 2.1 months, and median overall survival was 8 months. Conclusion Pembrolizumab exhibited clinically meaningful antitumor activity and an acceptable safety profile in recurrent/metastatic head and neck squamous cell carcinoma previously treated with platinum and cetuximab.
This study examines differences in the surface black carbon (BC) aerosol loading between the Bay of Bengal (BoB) and the Arabian Sea (AS) and identifies dominant sources of BC in South Asia and ...surrounding regions during March-May 2006 (Integrated Campaign for Aerosols, Gases and Radiation Budget, ICARB) period. A total of 13 BC tracers are introduced in the Weather Research and Forecasting Model coupled with Chemistry to address these objectives. The model reproduced the temporal and spatial variability of BC distribution observed over the AS and the BoB during the ICARB ship cruise and captured spatial variability at the inland sites. In general, the model underestimates the observed BC mass concentrations. However, the model-observation discrepancy in this study is smaller compared to previous studies. Model results show that ICARB measurements were fairly well representative of the AS and the BoB during the pre-monsoon season. Elevated BC mass concentrations in the BoB are due to 5 times stronger influence of anthropogenic emissions on the BoB compared to the AS. Biomass burning in Burma also affects the BoB much more strongly than the AS. Results show that anthropogenic and biomass burning emissions, respectively, accounted for 60 and 37% of the average plus or minus standard deviation (representing spatial and temporal variability) BC mass concentration (1341 plus or minus 2353 ng m-3) in South Asia. BC emissions from residential (61%) and industrial (23%) sectors are the major anthropogenic sources, except in the Himalayas where vehicular emissions dominate. We find that regional-scale transport of anthropogenic emissions contributes up to 25% of BC mass concentrations in western and eastern India, suggesting that surface BC mass concentrations cannot be linked directly to the local emissions in different regions of South Asia.
Wildfires have been increasing in frequency in the western United States (US) with the 2017 and 2018 fire seasons experiencing some of the worst wildfires in terms of suppression costs and air ...pollution that the western US has seen. Although growing evidence suggests respiratory exacerbations from elevated fine particulate matter (PM2.5) during wildfires, significantly less is known about the impacts on human health of ozone (O3) that may also be increased due to wildfires. Using machine learning, we created daily surface concentration maps for PM2.5 and O3 during an intense wildfire in California in 2008. We then linked these daily exposures to counts of respiratory hospitalizations and emergency department visits at the ZIP code level. We calculated relative risks of respiratory health outcomes using Poisson generalized estimating equations models for each exposure in separate and mutually-adjusted models, additionally adjusted for pertinent covariates. During the active fire periods, PM2.5 was significantly associated with exacerbations of asthma and chronic obstructive pulmonary disease (COPD) and these effects remained after controlling for O3. Effect estimates of O3 during the fire period were non-significant for respiratory hospitalizations but were significant for ED visits for asthma (RR = 1.05 and 95% CI = (1.022, 1.078) for a 10 ppb increase in O3). In mutually-adjusted models, the significant findings for PM2.5 remained whereas the associations with O3 were confounded. Adjusted for O3, the RR for asthma ED visits associated with a 10 μg/m3 increase in PM2.5 was 1.112 and 95% CI = (1.087, 1.138). The significant findings for PM2.5 but not for O3 in mutually-adjusted models is likely due to the fact that PM2.5 levels during these fires exceeded the 24-hour National Ambient Air Quality Standard (NAAQS) of 35 μg/m3 for 4976 ZIP-code days and reached levels up to 6.073 times the NAAQS, whereas our estimated O3 levels during the fire period only occasionally exceeded the NAAQS of 70 ppb with low exceedance levels. Future studies should continue to investigate the combined role of O3 and PM2.5 during wildfires to get a more comprehensive assessment of the cumulative burden on health from wildfire smoke.
•Ozone was associated with respiratory ED visits during a wildfire, but associations disappeared when adjusted for PM2.5•PM2.5 was associated with respiratory ED visits and hospitalizations during a wildfire period even when adjusted for ozone.•Our findings may be context specific; other wildfire-health studies should examine other air pollutants besides PM2.5
Summary Background We aimed to improve the outcomes for locoregionally advanced nasopharyngeal carcinoma by testing the feasibility and safety of the addition of bevacizumab to chemoradiotherapy. ...Methods We enrolled patients older than 18 years with stage IIB–IVB nasopharyngeal carcinoma from 19 centres in North America and Hong Kong. Treatment consisted of three cycles of bevacizumab (15 mg/kg) and cisplatin (100 mg/m2 ) both given on days 1, 22, and 43 of radiation (70 Gy) with intensity-modulated radiation therapy delivered over 33 days on a daily basis, Monday through Friday. Patients then received three cycles of bevacizumab (15 mg/kg) and cisplatin (80 mg/m2 ), both given on days 64, 85, and 106 after radiation, and three cycles of fluorouracil (1000 mg/m2 per day), given on days 64–67, 85–88, and 106–109 after radiation. The primary endpoint was the occurrence of treatment-related grade 4 haemorrhage or any grade 5 adverse event in the first year. Analyses were done with all eligible patients who started protocol treatment. The trial is registered at ClinicalTrials.gov , number NCT00408694. Findings From Dec 13, 2006, to Feb 5, 2009, we enrolled 46 patients, of whom 44 were eligible for analysis. We recorded no grade 3–4 haemorrhages or grade 5 adverse events; nine patients (20%) had a treatment-related grade 1–2 haemorrhage. Nine patients had one or more grade 4 blood or bone marrow-related complication (grade 4 leucopenia was noted in six patients, grade 4 lymphopenia in five, grade 4 neutrophils in five, and grade 4 anaemia in one). One patient had two grade 4 infections with grade 3–4 neutrophils. One patient reported grade 4 tinnitus, one patient reported grade 4 thrombosis, one reported grade 4 radiation mucositis, and two reported grade 4 pharyngolaryngeal pain. With a median follow-up of 2·5 years (IQR 2·1–2·9), the estimated 2 year locoregional progression-free interval was 83·7% (95% CI 72·6–94·9), the 2 year distant metastasis-free interval was 90·8% (82·2–99·5), the 2 year progression-free survival was 74·7% (61·8–87·6), and 2 year overall survival was 90·9% (82·3–99·4). Interpretation The addition of bevacizumab to standard chemoradiation treatment for patients with nasopharyngeal carcinoma is feasible, and might delay the progression of subclinical distant disease. Funding National Cancer Institute, USA.
This study presents annual simulations of tropospheric ozone and related species made for the first time using the WRF-Chem model over South Asia for the year 2008. The model-simulated ozone, CO, and ...NOx are evaluated against ground-based, balloon-borne and satellite-borne (TES, OMI and MOPITT) observations. The comparison of model results with surface ozone observations from seven sites and CO and NOx observations from three sites indicate the model's ability in reproducing seasonal variations of ozone and CO, but show some differences in NOx. The modeled vertical ozone distribution agrees well with the ozone soundings data from two Indian sites. The vertical distributions of TES ozone and MOPITT CO are generally well reproduced, but the model underestimates TES ozone, OMI tropospheric column NO2 and MOPITT total column CO retrievals during all the months, except MOPITT retrievals during August–January and OMI retrievals during winter. Largest differences between modeled and satellite-retrieved quantities are found during spring when intense biomass burning activity occurs in this region. The evaluation results indicate large uncertainties in anthropogenic and biomass burning emission estimates, especially for NOx. The model results indicate clear regional differences in the seasonality of surface ozone over South Asia, with estimated net ozone production during daytime (1130–1530 h) over inland regions of 0–5 ppbv h−1 during all seasons and of 0–2 ppbv h−1 over marine regions during outflow periods. The model results indicate that ozone production in this region is mostly NOx-limited. This study shows that WRF-Chem model captures many important features of the observations and gives confidence to using the model for understanding the spatio-temporal variability of ozone over South Asia. However, improvements of South Asian emission inventories and simulations at finer model resolution, especially over the complex Himalayan terrain in northern India, are also essential for accurately simulating ozone in this region.
This study quantifies the impact of the fires in California in fall 2007 on regional air quality and especially on surface ozone by analyzing surface observations of ozone concentrations together ...with global chemistry transport model simulations. The latter include a synthetic tracer providing information about the amount of ozone produced from the fires. It is shown that the global model is well suited for simulating the overall fire impact and a valuable tool for extracting information about the fire influence from the observations. A clear increase in observed ozone is found when the model predicts a strong impact of pollution from the fires, where measured afternoon 8‐hour concentrations increased, on average, by about 10 ppb. The findings demonstrate that intense wildfire periods can significantly increase the frequency of ozone concentrations exceeding current U.S. health standards, and might cause violations also during photochemically less active seasons. The study also demonstrates the far‐reaching impact of ozone production from the fires.
Metastatic thyroid cancers that are refractory to radioiodine (iodine-131) are associated with a poor prognosis. In mouse models of thyroid cancer, selective mitogen-activated protein kinase (MAPK) ...pathway antagonists increase the expression of the sodium-iodide symporter and uptake of iodine. Their effects in humans are not known.
We conducted a study to determine whether the MAPK kinase (MEK) 1 and MEK2 inhibitor selumetinib (AZD6244, ARRY-142886) could reverse refractoriness to radioiodine in patients with metastatic thyroid cancer. After stimulation with thyrotropin alfa, dosimetry with iodine-124 positron-emission tomography (PET) was performed before and 4 weeks after treatment with selumetinib (75 mg twice daily). If the second iodine-124 PET study indicated that a dose of iodine-131 of 2000 cGy or more could be delivered to the metastatic lesion or lesions, therapeutic radioiodine was administered while the patient was receiving selumetinib.
Of 24 patients screened for the study, 20 could be evaluated. The median age was 61 years (range, 44 to 77), and 11 patients were men. Nine patients had tumors with BRAF mutations, and 5 patients had tumors with mutations of NRAS. Selumetinib increased the uptake of iodine-124 in 12 of the 20 patients (4 of 9 patients with BRAF mutations and 5 of 5 patients with NRAS mutations). Eight of these 12 patients reached the dosimetry threshold for radioiodine therapy, including all 5 patients with NRAS mutations. Of the 8 patients treated with radioiodine, 5 had confirmed partial responses and 3 had stable disease; all patients had decreases in serum thyroglobulin levels (mean reduction, 89%). No toxic effects of grade 3 or higher attributable by the investigators to selumetinib were observed. One patient received a diagnosis of myelodysplastic syndrome more than 51 weeks after radioiodine treatment, with progression to acute leukemia.
Selumetinib produces clinically meaningful increases in iodine uptake and retention in a subgroup of patients with thyroid cancer that is refractory to radioiodine; the effectiveness may be greater in patients with RAS-mutant disease. (Funded by the American Thyroid Association and others; ClinicalTrials.gov number, NCT00970359.).
PDF
