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Mobile monitoring can supplement regulatory measurements, particularly in low-income countries where stationary monitoring is sparse. Here, we report results from a ~ year-long mobile monitoring campaign of on-road concentrations of black carbon (BC), ultrafine particles (UFP), and carbon dioxide (CO 2 ) in Bengaluru, India. The study route included 150 unique kms (average: ~22 repeat measurements per monitored road segment). After cleaning the data for known instrument artifacts and sensitivities, we generated 30 m high-resolution stable 'data only' spatial maps of BC, UFP, and CO 2 for the study route. For the urban residential areas, the mean BC levels for residential roads, arterials, and highways were ~ 10, 22, and 56 μg m -3 , respectively. A similar pattern (highways being characterized by highest pollution levels) was also observed for UFP and CO 2 . Using the data from repeat measurements, we carried out a Monte Carlo subsampling analysis to understand the minimum number of repeat measures to generate stable maps of pollution in the city. Leveraging the simultaneous nature of the measurements, we also mapped the quasi-emission factors (QEF) of the pollutants under investigation. The current study is the first multi-season mobile monitoring exercise conducted in a low or middle -income country (LMIC) urban setting that oversampled the study route and investigated the optimum number of repeat rides required to achieve representative pollution spatial patterns characterized with high precision and low bias. Finally, the results are discussed in the context of technical aspects of the campaign, limitations, and their policy relevance for our study location and for other locations. Given the day-to-day variability in the pollution levels, the presence of dynamic and unorganized sources, and active government pollution mitigation policies, multi-year mobile measurement campaigns would help test the long-term representativeness of the current results., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The societal costs of air pollution have historically been measured in terms of premature deaths (including the corresponding values of statistical lives lost), disability-adjusted life years, and medical costs. Emerging research, however, demonstrated potential impacts of air pollution on human capital formation. Extended contact with pollutants such as airborne particulate matter among young persons whose biological systems are still developing can result in pulmonary, neurobehavioral, and birth complications, hindering academic performance as well as skills and knowledge acquisition. Using a dataset that tracks 2014-2015 incomes for 96.2% of Americans born between 1979 and 1983, we assessed the association between childhood exposure to fine particulate matter (PM 2.5 ) and adult earnings outcomes across U.S. Census tracts. After accounting for pertinent economic covariates and regional random effects, our regression models indicate that early-life exposure to PM 2.5 is associated with lower predicted income percentiles by mid-adulthood; all else equal, children raised in high pollution tracts (at the 75th percentile of PM 2.5 ) are estimated to have approximately a 0.51 decrease in income percentile relative to children raised in low pollution tracts (at the 25th percentile of PM 2.5 ). For a person earning the median income, this difference corresponds to a $436 lower annual income (in 2015 USD). We estimate that 2014-2015 earnings for the 1978-1983 birth cohort would have been ∼$7.18 billion higher had their childhood exposure met U.S. air quality standards for PM 2.5 . Stratified models show that the relationship between PM 2.5 and diminished earnings is more pronounced for low-income children and for children living in rural environments. These findings raise concerns about long-term environmental and economic justice for children living in areas with poor air quality where air pollution could act as a barrier to intergenerational class equity., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors declare no known competing interests. Potential perceived competing interests include grant funding (e.g., Robert Wood Johnson Foundation, High TideFoundation, NIH, HEI, EPA)., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The widespread and rapid social and economic changes from Covid-19 response might be expected to dramatically improve air quality. However, national monitoring data from the US Environmental Protection Agency for criteria pollutants (PM 2.5 , ozone, NO 2 , CO, PM 10 ) provide inconsistent support for that expectation. Specifically, during stay-at-home orders, average PM 2.5 levels were slightly higher (~10% of its multi-year interquartile range [IQR]) than expected; average ozone, NO 2 , CO, and PM 10 levels were slightly lower (~30%, ~20%, ~27%, and ~1% of their IQR, respectively) than expected. The timing of peak anomaly, relative to the stay-at-home orders, varied by pollutant (ozone: 2 weeks before; NO 2 , CO: 3 weeks after; PM 10 : 2 weeks after); but, by 5-6 weeks after stay-at-home orders, the concentration anomalies appear to have ended. For PM 2.5 , ozone, CO, and PM 10 , no US state had lower-than-expected pollution levels for all weeks during stay-at-home-orders; for NO 2 , only Arizona had lower-than-expected levels for all weeks during stay-at-home orders. Our findings show that the enormous changes from the Covid-19 response have not lowered PM 2.5 levels across the US beyond their normal range of variability; for ozone, NO 2 , CO, and PM 10 concentrations were lowered but the reduction was modest and transient., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier B.V.)

Poly[di(carboxylatomethylphenoxy)phosphazene] (PCMP), a new member of polyphosphazene immunoadjuvant family, is synthesized. In vitro assessment of a new macromolecule revealed hydrolytic degradation profile and immunostimulatory activity comparable to its clinical stage homologue PCPP; however, PCMP was characterized by a beneficial reduced sensitivity to the ionic environment. In vivo evaluation of PCMP potency was conducted with human papillomavirus (HPV) virus-like particles (VLPs) based RG1-VLPs vaccine. In contrast with previously reported self-assembly of polyphosphazene adjuvants with proteins, which typically results in the formation of complexes with multimeric display of antigens, PCMP surface modified VLPs in a composition dependent pattern, which at a high polymer-to VLPs ratio led to stabilization of antigenic particles. Immunization experiments in mice demonstrated that PCMP adjuvanted RG1-VLPs vaccine induced potent humoral immune responses, in particular, on the level of highly desirable protective cross-neutralizing antibodies, and outperformed PCPP and Alhydrogel adjuvanted formulations., (Copyright © 2021 Elsevier Inc. All rights reserved.)

We conducted an emission measurement campaign as a part of a multiyear cookstove intervention trial in two rural locations in northern and southern India. 253 uncontrolled cooking tests measured emissions in control and intervention households during three ~3-month-long measurement periods in each location. We measured pollutants including fine particulate matter (PM 2.5 ), organic and elemental carbon (OC, EC), black carbon (BC) and carbon monoxide (CO) from stoves ranging from traditional solid fuel (TSF) to improved biomass stoves (rocket, gasifier) to liquefied petroleum gas (LPG) models. TSF stoves showed substantial variability in pollutant emission factors (EFs; g kg -1 wood) and optical properties across measurement periods. Multilinear regression modeling found that measurement period, fuel properties, relative humidity, and cooking duration are significant predictors of TSF EFs. A rocket stove showed moderate reductions relative to TSF. LPG stoves had the lowest pollutant EFs, with mean PM 2.5 and CO EFs (g MJ delivered -1 ) >90% lower than biomass stoves. However, in-home EFs of LPG were substantially higher than lab EFs, likely influenced by non-ideal combustion performance, emissions from food and possible influence from other combustion sources. In-home emission measurements may depict the actual exposure benefits associated with dissemination of LPG stoves in real world interventions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Formate can be incorporated into 10-formyl-tetrahydrofolate (10-formyl-THF), which is a substrate for purine synthesis, and after further reduction of the one-carbon group, may be used as a substrate for thymidylate synthesis and for homocysteine remethylation., Objective: We examined plasma formate concentrations and the expression of genes involved in the production and utilization of formate in fetal and neonatal rats and in pregnant and virgin female rats., Methods: In 1 experiment, plasma formate was measured by GC-MS in rats aged 1-56 d. In a second experiment, virgin female (adult) rats, 19-d pregnant rats (P) and their male and female fetuses (F), and 3-d-old (N) and 7-d-old (J) offspring had plasma and amniotic fluid analyzed for formate by GC-MS, mRNA abundance in liver and placenta by qPCR, and several plasma amino acids by HPLC., Results: The plasma formate concentration was significantly higher in fetuses at embryonic day 19 than in the mothers. It was also significantly higher in neonatal rats but slowly returned to adult concentrations by ∼3 wk. The abundance of mitochondrial monofunctional 10-formyl-tetrahydrofolate synthetase (Mthfd1l) mRNA was significantly higher in placenta (PP) and F liver than in liver of N or J. Expression of mitochondrial bifunctional NAD-dependent methylene-tetrahydrofolate dehydrogenase/methenyl-tetrahydrofolate cyclohydrolase (Mthfd2) was significantly enriched in PP and liver of P, intermediate in F liver, and much lower in liver of N and J, relative to PP. Serine hydroxymethyltransferase 2 (Shmt2), methylenetetrahydrofolate dehydrogenase 1 (Mthfd1), and glycine decarboxylase protein of the glycine cleavage system (Gldc) mRNA expression was significantly lower in PP compared with other groups. Cytoplasmic NAD(P)-dependent 10-formyl-tetrahydrofolate dehydrogenase (Aldh1/1) and mitochondrial NAD(P)-dependent 10-formyl-tetrahydrofolate dehydrogenase (Aldh1/2) , genes responsible for the catabolism of 10-formylTHF, were very weakly expressed in PP, low in livers of F and N, and reached the significantly higher adult levels in J. Serine, glycine, and methionine concentrations in plasma of F were significantly higher than in plasma of P., Conclusions: Formate metabolism is highly active in fetuses and in placenta of pregnant rats., (Copyright © The Author(s) 2020.)

Characterizing personal exposure to air temperature is critical to understanding exposure measurement error in epidemiologic studies using fixed-site exposure data and to identify strategies to protect public health. To date, no study evaluating personal air temperature in the general population has been conducted in a low-and-middle income country. We used data from the CHAI study consisting of 50 adults monitored in up to six non-consecutive 24 h sessions in peri-urban south India. We quantified the agreement and association between fixed-site ambient and personal air temperature, and identified predictors of personal air temperature based on housing assessment, self-reported, GPS, remote sensing, and wearable camera data. Mean (SD) daytime (6 am-10 pm) average personal air temperature was 31.2 (2.6) °C and mean nighttime (10 pm-6 am) average temperature was 28.8 (2.8) °C. Agreement between average personal air and fixed-site ambient temperatures was limited, especially at night when personal air temperatures were underestimated by fixed-site temperatures (MBE = -5.6 °C). The proportion of average personal nighttime temperature variability explained by ambient fixed-site temperatures was moderate (R 2 mar  = 0.39); daytime associations were stronger for women (R 2 mar  = 0.51) than for men (R 2 mar  = 0.3). Other predictors of average nighttime personal air temperature included residential altitude, ceiling height, and household income. Predictors of average daytime personal air temperature included roof materials, GPS-tracked altitude, time working in agriculture (for women), and time travelling (for men). No biomass cooking, urban heat island, or greenspace effects were identified. R 2 mar between ambient fixed-site and personal air temperature indicate that ambient fixed-site temperature is only a moderately useful proxy of personal air temperature in the context of peri-urban India. Our findings suggest that people living in houses at lower altitude, with lower ceiling height and asbestos roofing sheets might be more vulnerable to heat. We also identified households with higher income, women working in agriculture and men with long commutes as disproportionately exposed to high temperatures., (Copyright © 2019. Published by Elsevier B.V.)

An important component of air quality engineering is quantifying in-use, fleet-average emission factors, and the spatial patterns of vehicle emissions. We report here that an absolute principal component score (APCS) analysis of on-road mobile measurements is a straightforward, efficient method for identifying the major contributors of traffic-related pollutants, deriving fuel-based emission factors, and mapping spatial patterns. Specifically, we applied the APCS model to on-highway measurements of nitrogen oxides (NO X ), carbon monoxide (CO), carbon dioxide (CO 2 ), black carbon (BC), and particle number (PN) obtained from a mobile platform deployed over a 5-day sampling period in Chengdu, China. Data were collected for (1) heavy-duty diesel truck (HDDT) plumes ("chase data") and (2) the general on-road environment ("non-chase data"). The bootstrapped APCS model was used to estimate area-wide, fuel-based average emission factors and their respective 95% confidence intervals. Two components representing diesel trucks and gasoline vehicles were extracted from non-chase data, accounting for 67% of the variance of the on-highway concentrations. Two additional principal components extracted from HDDT chase data, representing normal and high emission features, further separating the emissions characteristics of HDDTs. The fleet-average emission factors for NO X , CO, BC, and PN were 2.2, 50.3, 0.023 g/kg, and 0.32 × 10 15 particles/kg for gasoline-powered vehicles, respectively; 33, 3.7, 0.19 g/kg, and 3.3 × 10 15 particles/kg fuel for HDDTs' normal emission feature, respectively; and 105, 29, 2.5 g/kg fuel, and 16 × 10 15 particles/kg fuel for HDDTs' high emission feature, respectively. APCS results for chase data revealed the existence of high emitters among Chengdu's HDDT fleet, with emission factors 3 to 13 times higher than the normal HDDT vehicles. Although the high emitters are a minority of the fleet, they disproportionately contribute to the overall emissions; emission control policies may wish to target such vehicles., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Outdoor air pollution is a major killer worldwide and the fourth largest contributor to the burden of disease in China. China is the most populous country in the world and also has the largest number of air pollution deaths per year, yet the spatial resolution of existing national air pollution estimates for China is generally relatively low. We address this knowledge gap by developing and evaluating national empirical models for China incorporating land-use regression (LUR), satellite measurements, and universal kriging (UK). Land use, traffic and meteorological variables were included for model building. We tested the resulting models in several ways, including (1) comparing models developed using forward variable selection vs. partial least squares (PLS) variable reduction, (2) comparing models developed with and without satellite measurements, and with and without UK, and (3) 10-fold cross-validation (CV), Leave-One-Province-Out CV (LOPO-CV), and Leave-One-City-Out CV (LOCO-CV). Satellite data and kriging are complementary in making predictions more accurate: kriging improved the models in well-sampled areas; satellite data substantially improved performance at locations far away from monitors. Variable-selection models performed similarly to PLS models in 10-fold CV, but better in LOPO-CV. Our best models employed forward variable selection and UK, with 10-fold CV R 2 of 0.89 (for both 2014 and 2015) for PM 2.5 and of 0.73 (year-2014) and 0.78 (year-2015) for NO 2 . Population-weighted concentrations during 2014-2015 decreased for PM 2.5 (58.7 μg/m 3 to 52.3 μg/m 3 ) and NO 2 (29.6 μg/m 3 to 26.8 μg/m 3 ). We produced the first high resolution national LUR models for annual-average concentrations in China. Models were applied on 1 km grid to support future research. In 2015, >80% of the Chinese population lived in areas that exceeded the Chinese national PM 2.5 standard, 35 μg/m 3 . Results here will be publicly available and may be useful for epidemiology, risk assessment, and environmental justice research., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Air pollution from cooking with solid fuels is a potentially modifiable risk factor for increased blood pressure and may lead to eye irritation., Objectives: To evaluate whether a climate motivated cookstove intervention reduced blood pressure and eye irritation symptoms in Indian women., Methods: Households using traditional stoves were randomized to receive a rocket stove or continue using traditional stoves. Systolic (SBP) and diastolic blood pressure (DBP), and self-reported eye symptoms were measured twice, pre-intervention and at least 124 days post-intervention in women > 25 years old in control (N = 111) and intervention (N = 111) groups in rural Karnataka, India. Daily (24-h) fine particle (PM 2.5 ) mass and absorbance (Abs) were measured in cooking areas at each visit. Mixed-effect models were used to estimate before-and-after differences in SBP, DBP and eye symptoms., Results: We observed a lower SBP (-2.0 (-4.5, 0.5) mmHg) and DBP (-1.1 (-2.9, 0.6) mmHg) among exclusive users of intervention stove, although confidence intervals included zero. Stacking or mixed use of intervention and traditional stoves contributed to a small increase in SBP 2.6 (-0.4, 5.7) mmHg) and DBP (1.2 (-0.9, 3.3) mmHg). Exclusive and mixed stove users experienced higher post-intervention reductions, on average, in self-reported eye irritation symptoms for burning sensation in eyes, and eyes look red often compared to control. Median air pollutant concentrations increased post-intervention in all stove groups, with the lowest median PM 2.5 increase in the exclusive intervention stove group., Conclusions: Health benefits were limited due to stacking and lower-than-predicted efficiency of the intervention stove in the field. Stove adoption and use behavior, in addition to stove technology, affects achievement of health co-benefits. Carbon-financing schemes need to align with international guidelines that have been set based on health outcomes to maximize health co-benefits from cookstove interventions., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Land-use regression (LUR) has been used to model local spatial variability of particulate matter in cities of high-income countries. Performance of LUR models is unknown in less urbanized areas of low-/middle-income countries (LMICs) experiencing complex sources of ambient air pollution and which typically have limited land use data. To address these concerns, we developed LUR models using satellite imagery (e.g., vegetation, urbanicity) and manually-collected data from a comprehensive built-environment survey (e.g., roads, industries, non-residential places) for a peri-urban area outside Hyderabad, India. As part of the CHAI (Cardiovascular Health effects of Air pollution in Telangana, India) project, concentrations of fine particulate matter (PM 2.5 ) and black carbon were measured over two seasons at 23 sites. Annual mean (sd) was 34.1 (3.2) μg/m 3 for PM 2.5 and 2.7 (0.5) μg/m 3 for black carbon. The LUR model for annual black carbon explained 78% of total variance and included both local-scale (energy supply places) and regional-scale (roads) predictors. Explained variance was 58% for annual PM 2.5 and the included predictors were only regional (urbanicity, vegetation). During leave-one-out cross-validation and cross-holdout validation, only the black carbon model showed consistent performance. The LUR model for black carbon explained a substantial proportion of the spatial variability that could not be captured by simpler interpolation technique (ordinary kriging). This is the first study to develop a LUR model for ambient concentrations of PM 2.5 and black carbon in a non-urban area of LMICs, supporting the applicability of the LUR approach in such settings. Our results provide insights on the added value of manually-collected built-environment data to improve the performance of LUR models in settings with limited data availability. For both pollutants, LUR models predicted substantial within-village variability, an important feature for future epidemiological studies., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Exposure to household air pollution is a leading cause of morbidity and mortality globally. However, due to the lack of validated low-cost monitors with long-lasting batteries in indoor environments, most epidemiologic studies use self-reported data or short-term household air pollution assessments as proxies of long-term exposure. We evaluated the performance of three low-cost monitors measuring fine particulate matter (PM 2.5 ) and carbon monoxide (CO) in a wood-combustion experiment conducted in one household of Spain for 5 days (including the co-location of 2 units of HAPEX and 3 units of TZOA-R for PM 2.5 and 3 units of EL-USB-CO for CO; a total of 40 unit-days). We used Spearman correlation (ρ) and Concordance Correlation Coefficient (CCC) to assess accuracy of low-cost monitors versus equivalent research-grade devices. We also conducted a field study in India for 1 week (including HAPEX in 3 households and EL-USB-CO in 4 households; a total of 49 unit-days). Correlation and agreement at 5-min were moderate-high for one unit of HAPEX (ρ = 0.73 / CCC = 0.59), for one unit of TZOA-R (ρ = 0.89 / CCC = 0.62) and for three units of EL-USB-CO (ρ = 0.82-0.89 / CCC = 0.66-0.91) in Spain, although the failure or malfunction rate among low-cost units was high in both settings (60% of unit-days in Spain and 43% in India). Low-cost monitors tested here are not yet ready to replace more established exposure assessment methods in long-term household air pollution epidemiologic studies. More field validation is needed to assess evolving sensors and monitors with application to health studies., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Assessing historical exposure to air pollution in epidemiological studies is often problematic because of limited spatial and temporal measurement coverage. Several methods for modelling historical exposures have been described, including land-use regression (LUR). Satellite-based LUR is a recent technique that seeks to improve predictive ability and spatial coverage of traditional LUR models by using satellite observations of pollutants as inputs to LUR. Few studies have explored its validity for assessing historical exposures, reflecting the absence of historical observations from popular satellite platforms like Aura (launched mid-2004). We investigated whether contemporary satellite-based LUR models for Australia, developed longitudinally for 2006-2011, could capture nitrogen dioxide (NO 2 ) concentrations during 1990-2005 at 89 sites around the country. We assessed three methods to back-extrapolate year-2006 NO 2 predictions: (1) 'do nothing' (i.e., use the year-2006 estimates directly, for prior years); (2) change the independent variable 'year' in our LUR models to match the years of interest (i.e., assume a linear trend prior to year-2006, following national average patterns in 2006-2011), and; (3) adjust year-2006 predictions using selected historical measurements. We evaluated prediction error and bias, and the correlation and absolute agreement of measurements and predictions using R 2 and mean-square error R 2 (MSE-R 2 ), respectively. We found that changing the year variable led to best performance; predictions captured between 41% (1991; MSE-R 2 = 31%) and 80% (2003; MSE-R 2 = 78%) of spatial variability in NO 2 in a given year, and 76% (MSE-R 2 = 72%) averaged over 1990-2005. We conclude that simple methods for back-extrapolating prior to year-2006 yield valid historical NO 2 estimates for Australia during 1990-2005. These results suggest that for the time scales considered here, satellite-based LUR has a potential role to play in long-term exposure assessment, even in the absence of historical predictor data., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Case Presentation: A woman in her 60s presented with 1 month of progressive dyspnea, watery rhinorrhea, and paroxysmal cough productive of clear, watery sputum. She was diagnosed with epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma at another institution 1 week prior to presentation and 3 weeks after the onset of symptoms. She was a never-smoker. She denied fevers and had completed a course of antibiotics for presumed pneumonia, without clinical improvement. She presented to the hospital due to increasing severity of her shortness of breath., (Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Personal exposure (PE) to air pollutants is driven by a combination of pollutant concentrations in indoor and outdoor environments, and time-activity pattern of individuals. The objectives of this study were to estimate personal exposure to PM 2.5 and black carbon (BC), and assess the representability of ambient air quality monitoring stations to serve as surrogates for PE in New Delhi. Personal exposure to air pollutants (PM 2.5-PE and BC PE ) was measured using portable, battery-operated instruments (PM 2.5 - pDR1500 and BC- microAethalometer AE51) in a small cohort of healthy adults (n=12 in summer, n=6 in winter) with no occupational exposure. Average PM 2.5-PE and BC PE (µg/m 3 ) were 53.9±136 and 3.71±4.29 respectively, in summer and 489.2±209.2 and 23.3±14.9 respectively, in winter. Activities associated with highest exposure levels were cooking and indoor cleaning for PM 2.5 , and commuting for BC. Within transport microenvironments, autorickshaws were found to be the most polluted, and lowest BC exposure was registered in public buses. Comparison of fixed-site ambient monitoring data showed a higher correlation with personal exposure dataset in winter compared to summer (r 2 of 0.51 (winter) and 0.21 (summer); 51% (winter) and 20% (summer)). This study highlights the need for detailed assessment of PE to air pollutants in Indian cities, and calls for a denser network of monitoring stations for better exposure assessment., (Copyright © 2017 Elsevier Inc. All rights reserved.)

To generate potent vaccine responses, subunit protein antigens typically require coformulation with an adjuvant. Oil-in-water emulsions are among the most widely investigated adjuvants, based on their demonstrated ability to elicit robust antibody and cellular immune responses in the clinic. However, most emulsions cannot be readily frozen or lyophilized, on account of the risk of phase separation, and may have a deleterious effect on protein antigen stability when stored long term as a liquid coformulation. To circumvent this, current emulsion-formulated vaccines generally require a complex multivial presentation with obvious drawbacks, making a single-vial presentation for such products highly desirable. We describe the development of a stable, lyophilized squalene emulsion adjuvant through innovative formulation and process development approaches. On reconstitution, freeze-dried emulsion preparations were found to have a minimal increase in particle size of ∼20 nm and conferred immunogenicity in BALB/c mice similar in potency to freshly prepared emulsion coformulations in liquid form., (Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Satellite-derived (SAT) and chemical transport model (CTM) estimates of PM 2.5 and NO 2 are increasingly used in combination with Land Use Regression (LUR) models. We aimed to compare the contribution of SAT and CTM data to the performance of LUR PM 2.5 and NO 2 models for Europe. Four sets of models, all including local traffic and land use variables, were compared (LUR without SAT or CTM, with SAT only, with CTM only, and with both SAT and CTM). LUR models were developed using two monitoring data sets: PM 2.5 and NO 2 ground level measurements from the European Study of Cohorts for Air Pollution Effects (ESCAPE) and from the European AIRBASE network. LUR PM 2.5 models including SAT and SAT+CTM explained ~60% of spatial variation in measured PM 2.5 concentrations, substantially more than the LUR model without SAT and CTM (adjR 2 : 0.33-0.38). For NO 2 CTM improved prediction modestly (adjR 2 : 0.58) compared to models without SAT and CTM (adjR 2 : 0.47-0.51). Both monitoring networks are capable of producing models explaining the spatial variance over a large study area. SAT and CTM estimates of PM 2.5 and NO 2 significantly improved the performance of high spatial resolution LUR models at the European scale for use in large epidemiological studies., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Alström syndrome is a clinically complex disorder characterized by progressive degeneration of sensory functions, resulting in visual and audiological impairment as well as metabolic disturbances. It is caused by recessively inherited mutations in the ALMS1 gene, which codes for a centrosomal/basal body protein. The purpose of this study was to investigate the genetic and clinical features of two Tunisian affected siblings with Alström syndrome. Detailed clinical examinations were performed including complete ophthalmic examination, serial audiograms and several biochemical and hormonal blood tests. For the molecular study, first genomic DNA was isolated using a standard protocol. Then, linkage analysis with microsatellite markers was performed and DNA array was used to detect known mutations. Subsequently, all ALMS1 exons were simultaneously sequenced for one affected patient with the TaGSCAN targeted sequencing panel. Finally, segregation of the causal variant was performed by Sanger sequencing. Both affected siblings had cone rod dystrophy with impaired visual acuity, sensorineural hearing loss and truncal obesity. One affected individual showed insulin resistance without diabetes mellitus. Other clinical features including cardiac and pulmonary dysfunction, hypothyroidism, hyperlipidemia, acanthosis nigricans, renal and hepatic dysfunction were absent. Genetic analysis showed the presence of a homozygous splice site mutation (c.10388-2A > G) in both affected siblings. Although Alström syndrome is relatively well characterized disease, this syndrome is probably misdiagnosed in Tunisia. Here, we describe the first report of Tunisian patients affected by this syndrome and carrying a homozygous ALMS1 mutation. The diagnosis was suspected after long-term clinical follow-up and confirmed by genetic testing., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

While laboratory studies show that air pollutants can potentiate insulin resistance, the epidemiologic evidence regarding the association of air pollution with diabetes incidence is conflicting. The purpose of the present study was to assess the association of the traffic-related nitrogen dioxide (NO2) with the incidence of diabetes in a longitudinal cohort study of African American women. We used Cox proportional hazards models to calculate hazard ratios and 95% confidence intervals (CI) for diabetes associated with exposure to NO2 among 43,003 participants in the Black Women's Health Study (BWHS). Pollutant levels at participant residential locations were estimated with 1) a land use regression model for participants living in 56 metropolitan areas, and 2) a dispersion model for participants living in 27 of the cities. From 1995 to 2011, 4387 cases of diabetes occurred. The hazard ratios per interquartile range of NO2 (9.7 ppb), adjusted for age, metropolitan area, education, vigorous exercise, body mass index, smoking, and diet, were 0.96 (95% CI 0.88-1.06) using the land use regression model estimates and 0.94 (95% CI 0.80, 1.10) using the dispersion model estimates. The present results do not support the hypothesis that exposure to NO2 contributes to diabetes incidence in African American women., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Almost half the world's population is exposed to household air pollution from biomass and coal combustion. The acute effects of household air pollution on the cardiovascular system are poorly characterized. We conducted a panel study of rural Indian women to assess whether personal exposures to black carbon during cooking were associated with acute changes in blood pressure., Methods: We enrolled 45 women (ages 25-66 years) who cooked with biomass fuels. During cooking sessions in winter and summer, we simultaneously measured their personal real-time exposure to black carbon and conducted ambulatory blood pressure measurements every 10min. We recorded ambient temperature and participants' activities while cooking. We assessed body mass index, socioeconomic status, and salt intake. Multivariate mixed effects regression models with random intercepts were used to estimate the associations between blood pressure and black carbon exposure, e.g., average exposure in the minutes preceding blood pressure measurement, and average exposure over an entire cooking session., Results: Women's geometric mean (GM) exposure to black carbon during cooking sessions was lower in winter (GM: 40μg/m(3); 95% CI: 30, 53) than in summer (GM: 56μg/m(3); 95% CI: 42, 76). Interquartile range increases in black carbon were associated with changes in systolic blood pressure from -0.4mm Hg (95% CI: -2.3, 1.5) to 1.9mm Hg (95% CI: -0.8, 4.7), with associations increasing in magnitude as black carbon values were assessed over greater time periods preceding blood pressure measurement. Interquartile range increases in black carbon were associated with small decreases in diastolic blood pressure from -0.9mm Hg (95% CI: -1.7, -0.1) to -0.4mm Hg (95% CI: -1.6, 0.8). Associations of a similar magnitude were estimated for cooking session-averaged values., Conclusions: We found some evidence of an association between exposure to black carbon and acute increases in systolic blood pressure in Indian women cooking with biomass fuels, which may have implications for the development of cardiovascular diseases., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Land-use regression (LUR) is a technique that can improve the accuracy of air pollution exposure assessment in epidemiological studies. Most LUR models are developed for single cities, which places limitations on their applicability to other locations. We sought to develop a model to predict nitrogen dioxide (NO2) concentrations with national coverage of Australia by using satellite observations of tropospheric NO2 columns combined with other predictor variables. We used a generalised estimating equation (GEE) model to predict annual and monthly average ambient NO2 concentrations measured by a national monitoring network from 2006 through 2011. The best annual model explained 81% of spatial variation in NO2 (absolute RMS error=1.4 ppb), while the best monthly model explained 76% (absolute RMS error=1.9 ppb). We applied our models to predict NO2 concentrations at the ~350,000 census mesh blocks across the country (a mesh block is the smallest spatial unit in the Australian census). National population-weighted average concentrations ranged from 7.3 ppb (2006) to 6.3 ppb (2011). We found that a simple approach using tropospheric NO2 column data yielded models with slightly better predictive ability than those produced using a more involved approach that required simulation of surface-to-column ratios. The models were capable of capturing within-urban variability in NO2, and offer the ability to estimate ambient NO2 concentrations at monthly and annual time scales across Australia from 2006-2011. We are making our model predictions freely available for research., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Alström Syndrome (ALMS) is an extremely rare multiorgan disease caused by mutations in ALMS1. Dilated cardiomyopathy (DCM) is a common finding but only one series has been investigated by Cardiac Magnetic Resonance (CMR)., Methods: Eight genetically proven ALMS patients (ages 11-41) underwent CMR performed by standard cine steady state, T1, T2 and late gadolinium enhancement (LGE) sequences. Ejection fraction (EF), Diastolic Volume (EDV) and Systolic Volume normalized for body surface area (ESV), and mass indices were determined, as well as EDV/Mass ratio, an index expressing the adequacy of cardiac mass to heart volume. Regional fibrosis was assessed by LGE; diffuse fibrosis was measured by a TI scout sequence acquired at 5, 10 and 15 min after gadolinium by comparing inversion time values (TI) at null time in ALMS and control group., Results: In one patient severe DCM was present with diffuse LGE. There were seven cases without clinical DCM. In these patients, EF was at lower normal limits or slightly reduced and ESV index increased; six patients had decreased mass index and EDV/Mass ratio. Mild regional non ischemic fibrosis was detected by LGE in three cases; diffuse fibrosis was observed in all cases, as demonstrated by shorter TI values in ALMS in comparison with controls (5 min: 152 ± 12 vs 186 ± 16, p 0.0002; 10 min: 175 ± 8 vs 204 ± 18, p 0.0012; 15 min: 193 ± 9 vs 224 ± 16, p 0.0002)., Conclusions: Cardiac involvement in ALMS is characterized by progressive DCM, associated with systolic dysfunction, myocardial fibrosis and reduced myocardial mass., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

We measured real-time exposure to PM(2.5), ultrafine PM (particle number) and carbon monoxide (CO) for commuting workers school children, and traffic police, in Jakarta, Indonesia. In total, we measured exposures for 36 individuals covering 93 days. Commuters in private cars experienced mean (st dev) exposures of 22 (9.4) ppm CO, 91 (38) μg/m(3)PM(2.5), and 290 (150)×10(3) particles cm(-3). Mean concentrations were higher in public transport than in private cars for PM(2.5) (difference in means: 22%) and particle counts (54%), but not CO, likely reflecting in-vehicle particle losses in private cars owing to air-conditioning. However, average commute times were longer for private car commuters than public transport commuters (in our sample, 24% longer: 3.0 vs. 2.3 h per day). Commute and traffic-related exposures experienced by Jakarta residents are among the highest in the world, owing to high on-road concentrations and multi-hour commutes., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: Allergen immunotherapy is effective in allergic individuals however efforts are being made to improve its safety, convenience, and efficacy. It has recently been demonstrated that allergen-linked immunostimulatory DNA (ISS) is effective in stimulating an allergen-specific Th1 response with decreased allergenicity. The objective of this study is to investigate whether ISS linked to purified ragweed allergen Amb-a-1 (AIC) can inhibit local allergen-specific Th2 and induce allergen-specific Th1 responses in explanted nasal mucosa of ragweed-sensitive subjects. In addition, we set out to determine whether AIC is more effective compared to stimulation with unlinked Amb a 1 and ISS., Methods: Tissue from ragweed-sensitive patients (n = 12) was cultured with whole ragweed allergen (RW), Amb-a-1, AIC, Amb-a-1 and ISS (unlinked), or tetanus toxoid (TT) for 24 hours. IL-4, -5, -13, TNF-alpha and IFN-gamma mRNA-positive cells were visualized by in situ hybridization and T cells, B cells and neutrophils were enumerated using immunocytochemistry., Results: RW or Amb-a-1 increased the number of IL-4, IL-5, and IL-13 mRNA+ cells in the tissue compared to medium alone. AIC had similar cytokine mRNA reactivity as control tissue. AIC and TT increased IFNgamma-mRNA expression. Unlinked Amb-a-1 and ISS showed similar effects to AIC, however this response was weaker. The number of TNF mRNA+ cells, T cells, B cells and neutrophils remained unchanged., Conclusions: AIC is effective in stimulating a local allergen-specific Th1- and abolishing Th2-cytokine mRNA reactivity in the nose and may be considered as a strong candidate for an improved approach to immunotherapy in ragweed-sensitive individuals.

The immunostimulatory effects of bacterial DNA on mammalian cells have been localized to unmethylated CpG motifs, and synthetic CpG-containing oligodeoxynucleotides that mimic these effects are known as immunostimulatory sequences (ISS). We have found that the polycationic antibiotic, polymyxin B (PMXB), associates with ISS and serum albumin in vitro and forms microparticles that greatly increase the activity of ISS on plasmacytoid dendritic cells (PDCs). Specifically, ISS/PMXB greatly enhanced IFN-alpha production from PDCs and other activities downstream of IFN-alpha, including IFN-gamma secretion, NK lytic activity, and the expression of genes dependent upon IFN-alpha/IFN-gamma. This amplification was specific for the IFN-alpha pathway since other ISS activities, including B cell proliferation, B cell IL-6 secretion, and PDC maturation, were not affected by PMXB. Both the polycationic peptide and lipophilic fatty acid side chain domains of PMXB, as well as the presence of a third party stabilizing agent such as albumin or Tween 85, were required for particle formation and enhanced ISS activity. The ISS-enhancing activity of PMXB was observed across multiple species (human, primate, and mouse) and in vivo (primate, mouse). These data illustrate the usefulness of formulating ISS with a cationic lipopeptide such as PMXB, which focuses and greatly amplifies the ISS-induced pathway of IFN-alpha-mediated responses.

Immunostimulatory sequences (ISS) are short oligonucleotides containing unmethylated cytosine-phosphate-guanine (CpG) dinucleotides that stimulate innate immune responses through Toll-like receptor-9 on B cells and plasmacytoid dendritic cell (PDC) precursors. The anti-inflammatory cytokine interleukin (IL)-10 is predicted to be a potent inhibitor of many of the activities described for ISS, and this may impact the use of ISS in disease states characterized by elevated IL-10. As the activities of ISS on PDCs are central to many clinical applications of ISS, we have studied the effects of IL-10 on PDC stimulation by 3 distinct classes of ISS. IL-10 inhibited cytokine production and survival of ISS-activated PDCs; however, IL-12 induction was much more sensitive to inhibition than interferon (IFN)-alpha induction. Within the PDC population are cells that respond to ISS by producing either IL-12 or IFN-alpha but not both cytokines. IL-12-producing PDCs require costimulation through CD40 and appear more mature than IFN-alpha-producing PDCs. The 3 distinct classes of ISS differed with respect to induction of PDC maturation and T-cell priming capacity. IL-10 regulated PDC activation but did not inhibit the subsequent T-cell-priming ability of PDCs already activated by ISS.

Interleukin-12 (IL-12) is a potentially critical factor in the immune response against human immunodeficiency virus (HIV) because it is important for regulating proliferation and interferon-gamma (IFN-gamma) production by T cells and natural killer (NK) cells, antigen presentation and accessory cell function by macrophages and dendritic cells, and cytolytic activities of cytotoxic T-lymphocyte cells and NK cells, which are all functions known to be dysfunctional in patients with acquired immune deficiency syndrome. Peripheral blood mononuclear cells (PBMC) from HIV-infected patients have been previously shown to be deficient in the ability to produce IL-12 in response to the bacterial pathogen Staphylococcus aureus Cowan. In this study, impaired IL-12 production in cells from PBMC of HIV-infected patients compared with healthy donors was observed across a broad panel of stimuli derived from infectious pathogens with or without priming with cytokines such as IFN-gamma and IL-4, which amplify the IL-12 induction signal. Analysis of p40 and p35 mRNA accumulation showed that reductions in both subunits contribute to the lower IL-12 secretion of cells from HIV-infected individuals. PBMC from HIV-infected donors also failed to upregulate the IL-12 receptor beta2 chain (IL-12Rbeta2) in response to mitogenic stimuli. The expression of the IL-12Rbeta2 gene could, however, be restored by in vitro exposure to rIL-12. Thus, it is possible that a primary IL-12 defect may lead to secondary deficiencies in expression of the genes for IL-12Rbeta2 and IFN-gamma, thus amplifying immune deficiency during HIV infection.

Although Th2 helper cell clones produce IL-4 and IL-5, CD4+ T cells taken fresh from lymphoid organs of mice produce IL-2 and some IFN-gamma, but not IL-4 or IL-5. The exact parameters that enhance the synthesis of IL-4, IL-5, and particularly IL-10 from resting antigen-specific CD4+ T cells is not yet clear. We therefore examined the kinetics of, and the parameters that affect, the development of IL-4, IL-5, and IL-10 production in bulk populations of antigen-specific human CD4+ T cells. We demonstrated that in vitro stimulation of human peripheral blood lymphocytes with antigen (tetanus toxoid or a viral antigen, Varicella zoster) for several days resulted in the production of IL-2 and IFN-gamma, but little or no IL-4 or IL-5. This cytokine profile was observed even when CD4+ T cells from allergic donors were stimulated once in vitro with allergen (rye grass pollen, Lolium perenne I, or dust mite allergen, Dermatophagoides farinae). The observed cytokine profile reflected that of the vast majority of antigen-specific T cells, since we studied the response of bulk populations of CD4+ T cells rather than that of a "selected" number of antigen-specific T cell clones. Furthermore, we observed that human CD4+ T cells from either allergic or nonallergic individuals failed to produce significant quantities of IL-4, IL-5, or IL-10 even after several rounds of stimulation with soluble protein (nonallergen) antigens such as tetanus toxoid or Var. z. However, large quantities of these cytokines were produced when stimulation of the T cells occurred in the presence of rIL-4, but only after two stimulations in vitro with antigen over a period of greater than 7 days. In addition, substantial quantities of IL-4, IL-5, and IL-10 were produced by CD4+ T cells from allergic subjects in the absence of exogenous IL-4, but only after two stimulations in vitro with allergens such as rye grass pollen or dust mite allergen. These results indicate that the development of IL-4 and IL-5 synthesis occurs in peripheral blood CD4+ T cells in a stepwise fashion, first with the production of IL-2 and IFN-gamma, and later with the production of IL-4 and IL-5.(ABSTRACT TRUNCATED AT 250 WORDS)

The opportunistic pathogen Pneumocystis carinii (Pc) poses a major clinical health problem in individuals with immune deficiency, including those patients with human immunodeficiency (HIV)-associated acquired immune deficiency disease (AIDS). Heretofore, in vivo investigations of the biology of Pc and pathogenesis of pneumocystosis have generally employed steroid-induced immune suppression with antibiotic prophylaxis and protein deprivation. This approach has many drawbacks, chief among them being the widespread, multiple interacting effects caused by the inducing agents. Athymic (nude) mice and rats have been used, but are less than ideal, as the immune defect primarily affects T lymphocytes. This article describes the natural history, pathobiology, and environmental effects on Pc pneumonitis in nonaxenically housed mice homozygous for the autosomal recessive mutation 'severe combined immunodeficiency' (scid), which almost totally lack both cell-mediated and antibody-mediated immune functions. The predictability, unequivocal expression, high morbidity, and well-defined genetic basis make scid/scid mutant mice the model of choice for in vivo studies of spontaneous pneumocystosis.

A comparative study of obesity measurements was undertaken with 533 male and female subjects, aged 11.8-15.9. Six adiposity measures (three skinfold indices, three height-weight indices) were derived from measures of height, weight, and eight skinfold thickness measurements. A principal components analysis of these adiposity measures resulted in a unifactorial solution accounting for 85.6% of the total variance. A cross-tabulation analysis with the derived factor scores and a criterion visual inspection rating supported the interpretation that the underlying construct of the factor was adiposity, and that a factor score of greater than 1.5 SD above the mean was a suitable standard for labeling obesity. Utilizing this dichotomy of factor scores as a standard, the differential diagnostic capabilities of four adiposity scales commonly used in identifying obesity was undertaken. Pursuit of this methodology, with the use of additional measures and larger sample sizes, is recommended to ensure the validation of an obesity measure.

Endocytosis in polyclonally activated, Con A-stimulated spleen cell cultures was analyzed. It was found that as lymphocytes differentiate to acquire cytotoxic capability their endocytic activity also increases, reaching a plateau at 48 hr. Inhibition of sterol synthesis reduced endocytic rates by as much as 50% when 25-hydroxycholesterol was added during the first 24 hr of culture, the time at which sterol synthesis is at its maximum. When 25-hydroxycholesterol was added after the cycle of sterol synthesis, little or no suppression of endocytosis was seen. Compactin, which is an allosteric, competitive inhibitor of HMG-CoA reductase (the rate-limiting enzyme in the sterol biosynthetic pathway), produced a similar abrogation of endocytic rate. The effect of inhibition of sterol synthesis on endocytosis can be counteracted by the addition of cholesterol to the cultures. It is hypothesized that the dynamic process of endocytosis plays a role in the reorganization of membrane components necessary for the expression of the differentiated state of cytotoxicity.