Designing health impact functions to assess marginal changes in outdoor fine particulate matter.

Estimating health benefits from improvements in ambient air quality requires the characterization of the magnitude and shape of the association between marginal changes in exposure and marginal changes in risk, and its uncertainty. Several attempts have been made to do this, each requiring different assumptions. These include the Log-Linear(LL), IntegratedExposure-Response(IER), and GlobalExposureMortalityModel(GEMM). In this paper we develop an improved relative risk model suitable for use in health benefits analysis that incorporates features of existing models while addressing limitations in each model. We model the derivative of the relative risk function within a meta-analytic framework; a quantity directly applicable to benefits analysis, incorporating a Fusion of algebraic functions used in previous models. We assume a constant derivative in concentration over low exposures, like the LL model, a declining derivative over moderate exposures observed in cohort studies, and a derivative declining as the inverse of concentration over high global exposures in a similar manner to the GEMM. The model properties are illustrated with examples of fitting it to data for the six specific causes of death previously examined by the GlobalBurdenofDisease program with ambient fine particulate matter (PM2.5). In a test case analysis assuming a 1% (benefits analysis) or 100% (burden analysis), reduction in country-specific fine particulate matter concentrations, corresponding estimated global attributable deaths using the Fusion model were found to lie between those of the IER and LL models, with the GEMM estimates similar to those based on the LL model.

The health impacts of Indonesian peatland fires.

BACKGROUND: Indonesian peatlands have been drained for agricultural development for several decades. This development has made a major contribution to economic development. At the same time, peatland drainage is causing significant air pollution resulting from peatland fires. Peatland fires occur every year, even though their extent is much larger in dry (El Niño) years. We examine the health effects of long-term exposure to fine particles (PM2.5) from all types of peatland fires (including the burning of above and below ground biomass) in Sumatra and Kalimantan, where most peatland fires in Indonesia take place. METHODS: We derive PM2.5 concentrations from satellite imagery calibrated and validated with Indonesian Government data on air pollution, and link increases in these concentrations to peatland fires, as observed in satellite imagery. Subsequently, we apply available epidemiological studies to relate PM2.5 exposure to a range of health outcomes. The model utilizes the age distribution and disease prevalence of the impacted population. RESULTS: We find that PM2.5 air pollution from peatland fires, causes, on average, around 33,100 adults and 2900 infants to die prematurely each year from air pollution. In addition, peatland fires cause on average around 4390 additional hospitalizations related to respiratory diseases, 635,000 severe cases of asthma in children, and 8.9 million lost workdays. The majority of these impacts occur in Sumatra because of its much higher population density compared to Kalimantan. A main source of uncertainty is in the Concentration Response Functions (CRFs) that we use, with different CRFs leading to annual premature adult mortality ranging from 19,900 to 64,800 deaths. Currently, the population of both regions is relatively young. With aging of the population over time, vulnerabilities to air pollution and health effects from peatland fires will increase. CONCLUSIONS: Peatland fire health impacts provide a further argument to combat fires in peatlands, and gradually transition to peatland management models that do not require drainage and are therefore not prone to fire risks.

Assessing the recent estimates of the global burden of disease for ambient air pollution: Methodological changes and implications for low- and middle-income countries.

The Global Burden of Disease (GBD) is a comparative assessment of the health impact of the major and well-established risk factors, including ambient air pollution (AAP) assessed by concentrations of PM2.5 (particles less than 2.5 µm) and ozone. Over the last two decades, major improvements have emerged for two important inputs in the methodology for estimating the impacts of PM2.5: the assessment of global exposure to PM2.5 and the development of integrated exposure risk models (IERs) that relate the entire range of global exposures of PM2.5 to cause-specific mortality. As a result, the estimated annual mortality attributed to AAP increased from less than 1 million in 2000 to roughly 3 million for GBD in years 2010 and 2013, to 4.2 million for GBD 2015. However, the magnitude of the recent change and uncertainty regarding its rationale have resulted, in some cases, in skepticism and reduced confidence in the overall estimates. To understand the underlying reasons for the change in mortality, we examined the estimates for the years 2013 and 2015 to determine the quantitative implications of alternative model input assumptions. We calculated that the year 2013 estimates increased by 8% after applying the updated exposure data used in GBD 2015, and increased by 23% with the application of the updated IERs from GBD 2015. The application of both upgraded methodologies together increased the GBD 2013 estimates by 35%, or about one million deaths. We also quantified the impact of the changes in demographics and the assumed threshold level. Since the global estimates of air pollution-related deaths will continue to change over time, a clear documentation of the modifications in the methodology and their impacts is necessary. In addition, there is need for additional monitoring and epidemiological studies to reduce uncertainties in the estimates for low- and medium-income countries, which contribute to about one-half of the mortality.

Valuing deaths or years of life lost? Economic benefits of avoided mortality from early heat warning systems.

The study aims to explore the main drivers influencing the economic appraisal of heat warning systems by integrating epidemiological modelling and benefit-cost analysis. To shed insights on heat wave mortality valuation, we consider three valuation schemes: (i) a traditional one, where the value of a statistical life (VSL) is applied to both displaced and premature mortality; (ii) an intermediate one, with VSL applied for premature mortality and value of a life year (VOLY) for displaced mortality; and (iii) a conservative one, where both premature and displaced mortality are quantified in terms of loss of life expectancy, and then valued using the VOLY approach. When applying these three schemes to Madrid (Spain), we obtain a benefit-cost ratio varying from 12 to 3700. We find that the choice of the valuation scheme has the largest influence, whereas other parameters such as attributable risk, displaced mortality ratio, or the comprehensiveness and effectiveness of the heat warning system are less influential. The results raise the question of which is the most appropriate approach to value mortality in the context of heat waves, given that the lower bound estimate for the benefit-cost ratio (option iii using VOLY) is up to two orders of magnitude lower than the value based on the traditional VSL approach (option i). The choice of the valuation methodology has significant implications for public health authorities at the local and regional scale, which becomes highly relevant for locations where the application of the VOLY approach could lead to benefit-cost ratios significantly lower than 1. We propose that specific metrics for premature and displaced VOLYs should be developed for the context of heat waves. Until such values are available, we suggest testing the economic viability of heat warning systems under the three proposed valuation schemes (i-iii) and using values for VOLY commonly applied in air pollution as the health end points are similar. Lastly, periodical reassessment of heat alert plans should be performed by public health authorities to monitor their long-term viability and cost-effectiveness.

Choices of morbidity outcomes and concentration-response functions for health risk assessment of long-term exposure to air pollution.

Background: Air pollution health risk assessment (HRA) has been typically conducted for all causes and cause-specific mortality based on concentration-response functions (CRFs) from meta-analyses that synthesize the evidence on air pollution health effects. There is a need for a similar systematic approach for HRA for morbidity outcomes, which have often been omitted from HRA of air pollution, thus underestimating the full air pollution burden. We aimed to compile from the existing systematic reviews and meta-analyses CRFs for the incidence of several diseases that could be applied in HRA. To achieve this goal, we have developed a comprehensive strategy for the appraisal of the systematic reviews and meta-analyses that examine the relationship between long-term exposure to particulate matter with an aerodynamic diameter smaller than 2.5 µm (PM2.5), nitrogen dioxide (NO2), or ozone (O3) and incidence of various diseases. Methods: To establish the basis for our evaluation, we considered the causality determinations provided by the US Environmental Protection Agency Integrated Science Assessment for PM2.5, NO2, and O3. We developed a list of pollutant/outcome pairs based on these assessments and the evidence of a causal relationship between air pollutants and specific health outcomes. We conducted a comprehensive literature search using two databases and identified 75 relevant systematic reviews and meta-analyses for PM2.5 and NO2. We found no relevant reviews for long-term exposure to ozone. We evaluated the reliability of these studies using an adaptation of the AMSTAR 2 tool, which assesses various characteristics of the reviews, such as literature search, data extraction, statistical analysis, and bias evaluation. The tool's adaptation focused on issues relevant to studies on the health effects of air pollution. Based on our assessment, we selected reviews that could be credible sources of CRF for HRA. We also assessed the confidence in the findings of the selected systematic reviews and meta-analyses as the sources of CRF for HRA. We developed specific criteria for the evaluation, considering factors such as the number of included studies, their geographical distribution, heterogeneity of study results, the statistical significance and precision of the pooled risk estimate in the meta-analysis, and consistency with more recent studies. Based on our assessment, we classified the outcomes into three lists: list A (a reliable quantification of health effects is possible in an HRA), list B+ (HRA is possible, but there is greater uncertainty around the reliability of the CRF compared to those included on list A), and list B- (HRA is not recommended because of the substantial uncertainty of the CRF). Results: In our final evaluation, list A includes six CRFs for PM2.5 (asthma in children, chronic obstructive pulmonary disease, ischemic heart disease events, stroke, hypertension, and lung cancer) and three outcomes for NO2 (asthma in children and in adults, and acute lower respiratory infections in children). Three additional outcomes (diabetes, dementia, and autism spectrum disorders) for PM2.5 were included in list B+. Recommended CRFs are related to the incidence (onset) of the diseases. The International Classification of Diseases, 10th revision codes, age ranges, and suggested concentration ranges are also specified to ensure consistency and applicability in an HRA. No specific suggestions were given for ozone because of the lack of relevant systematic reviews. Conclusion: The suggestions formulated in this study, including CRFs selected from the available systematic reviews, can assist in conducting reliable HRAs and contribute to evidence-based decision-making in public health and environmental policy. Future research should continue to update and refine these suggestions as new evidence becomes available and methodologies evolve.

Two Decades of Air Pollution Health Risk Assessment: Insights From the Use of WHO's AirQ and AirQ+ Tools.

Objectives: We evaluated studies that used the World Health Organization's (WHO) AirQ and AirQ+ tools for air pollution (AP) health risk assessment (HRA) and provided best practice suggestions for future assessments. Methods: We performed a comprehensive review of studies using WHO's AirQ and AirQ+ tools, searching several databases for relevant articles, reports, and theses from inception to Dec 31, 2022. Results: We identified 286 studies that met our criteria. The studies were conducted in 69 countries, with most (57%) in Iran, followed by Italy and India (∼8% each). We found that many studies inadequately report air pollution exposure data, its quality, and validity. The decisions concerning the analysed population size, health outcomes of interest, baseline incidence, concentration-response functions, relative risk values, and counterfactual values are often not justified, sufficiently. Many studies lack an uncertainty assessment. Conclusion: Our review found a number of common shortcomings in the published assessments. We suggest better practices and urge future studies to focus on the quality of input data, its reporting, and associated uncertainties.

New concentration-response functions for seven morbidity endpoints associated with short-term PM2.5 exposure and their implications for health impact assessment.

BACKGROUND: Morbidity burdens from ambient air pollution are associated with market and non-market costs and are therefore important for policymaking. The estimation of morbidity burdens is based on concentration-response functions (CRFs). Most existing CRFs for short-term exposures to PM2.5 assume a fixed risk estimate as a log-linear function over an extrapolated exposure range, based on evidence primarily from Europe and North America. OBJECTIVES: We revisit these CRFs by performing a systematic review for seven morbidity endpoints previously assessed by the World Health Organization, including data from all available regions. These endpoints include all cardiovascular hospital admission, all respiratory hospital admission, asthma hospital admission and emergency room visit, along with the outcomes that stem from morbidity, such as lost work days, respiratory restricted activity days, and child bronchitis symptom days. METHODS: We estimate CRFs for each endpoint, using both a log-linear model and a nonlinear model that includes additional parameters to better fit evidence from high-exposure regions. We quantify uncertainties associated with these CRFs through randomization and Monte Carlo simulations. RESULTS: The CRFs in this study show reduced model uncertainty compared with previous CRFs in all endpoints. The nonlinear CRFs produce more than doubled global estimates on average, depending on the endpoint. Overall, we assess that our CRFs can be used to provide policy analysis of air pollution impacts at the global scale. It is however important to note that improvement of CRFs requires observations over a wide range of conditions, and current available literature is still limited. DISCUSSION: The higher estimates produced by the nonlinear CRFs indicates the possibility of a large underestimation in current assessments of the morbidity impacts attributable to air pollution. Further studies should be pursued to better constrain the CRFs studied here, and to better characterize the causal relationship between exposures to PM2.5 and morbidity outcomes.

Reversal of trends in global fine particulate matter air pollution.

Ambient fine particulate matter (PM2.5) is the world's leading environmental health risk factor. Quantification is needed of regional contributions to changes in global PM2.5 exposure. Here we interpret satellite-derived PM2.5 estimates over 1998-2019 and find a reversal of previous growth in global PM2.5 air pollution, which is quantitatively attributed to contributions from 13 regions. Global population-weighted (PW) PM2.5 exposure, related to both pollution levels and population size, increased from 1998 (28.3 µg/m3) to a peak in 2011 (38.9 µg/m3) and decreased steadily afterwards (34.7 µg/m3 in 2019). Post-2011 change was related to exposure reduction in China and slowed exposure growth in other regions (especially South Asia, the Middle East and Africa). The post-2011 exposure reduction contributes to stagnation of growth in global PM2.5-attributable mortality and increasing health benefits per µg/m3 marginal reduction in exposure, implying increasing urgency and benefits of PM2.5 mitigation with aging population and cleaner air.

Intake fraction for particulate matter: recommendations for life cycle impact assessment.

Particulate matter (PM) is a significant contributor to death and disease globally. This paper summarizes the work of an international expert group on the integration of human exposure to PM into life cycle impact assessment (LCIA), within the UNEP/SETAC Life Cycle Initiative. We review literature-derived intake fraction values (the fraction of emissions that are inhaled), based on emission release height and "archetypal" environment (indoor versus outdoor; urban, rural, or remote locations). Recommended intake fraction values are provided for primary PM(10-2.5) (coarse particles), primary PM(2.5) (fine particles), and secondary PM(2.5) from SO(2), NO(x), and NH(3). Intake fraction values vary by orders of magnitude among conditions considered. For outdoor primary PM(2.5), representative intake fraction values (units: milligrams inhaled per kilogram emitted) for urban, rural, and remote areas, respectively, are 44, 3.8, and 0.1 for ground-level emissions, versus 26, 2.6, and 0.1 for an emission-weighted stack height. For outdoor secondary PM, source location and source characteristics typically have only a minor influence on the magnitude of the intake fraction (exception: intake fraction values can be an order of magnitude lower for remote-location emission than for other locations). Outdoor secondary PM(2.5) intake fractions averaged over respective locations and stack heights are 0.89 (from SO(2)), 0.18 (NO(x)), and 1.7 (NH(3)). Estimated average intake fractions are greater for primary PM(10-2.5) than for primary PM(2.5) (21 versus 15), owing in part to differences in average emission height (lower, and therefore closer to people, for PM(10-2.5) than PM(2.5)). For indoor emissions, typical intake fraction values are ∼1000-7000. This paper aims to provide as complete and consistent an archetype framework as possible, given current understanding of each pollutant. Values presented here facilitate incorporating regional impacts into LCIA for human health damage from PM.

Electromagnetic effects on forearm disuse osteopenia: a randomized, double-blind, sham-controlled study.

A randomized, double-blind, sham-controlled, feasibility and dosing study was undertaken to determine if a common pulsing electromagnetic field (PEMF) treatment could moderate the substantial osteopenia that occurs after forearm disuse. Ninety-nine subjects were randomized into four groups after a distal radius fracture, or carpal surgery requiring immobilization in a cast. Active or identical sham PEMF transducers were worn on the distal forearm for 1, 2, or 4 h/day for 8 weeks starting after cast removal ("baseline") when bone density continues to decline. Bone mineral density (BMD) and bone geometry were measured in the distal forearm by dual energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT) at entry ("baseline") and 8, 16, and 24 weeks later. Significant average BMD losses after baseline were observed in the affected forearm at all time points (5-7% distally and 3-4% for the radius/ulna shaft). However, after adjusting for age, gender, and baseline BMD there was no evidence of a positive effect of active versus sham PEMF treatment on bone loss by DXA or pQCT for subjects completing all visits (n = 82, ∼20 per group) and for an intent-to-treat analysis (n = 99). Regardless of PEMF exposure, serum bone-specific alkaline phosphatase (BSAP) was normal at baseline and 8 weeks, while serum c-terminal collagen teleopeptide (CTX-1) was markedly elevated at baseline and less so at 8 weeks. Although there was substantial variability in disuse osteopenia, these results suggested that the particular PEMF waveform and durations applied did not affect the continuing substantial disuse bone loss in these subjects.

Urban Municipal Solid Waste management: Modeling air pollution scenarios and health impacts in the case of Accra, Ghana.

Despite the clear link between air pollution and health, research to investigate the relationship between municipal solid waste management and air pollution and health has not been prioritized. Such research may generate scientific information that would help reduce population exposure to air pollutants. This paper examines the case study of Accra in Ghana, a city dealing with serious waste management problems. The paper proposes a methodology to estimate the impact of waste management on urban air pollution and health. The analysis is described in the following four steps: (1) collecting data on the waste sector; (2) modeling the emissions arising from waste management; (3) transforming emissions to concentration values and (4) estimating the burdens on health. The assessment has been conducted using the CCAC SWEET tool and WHO AirQ+. The method presented can be used in different locations, depending on data availability, when analyzing the impact of and potential changes to waste sector policies. The results of this health impact assessment indicate that, based on the emissions of PM2.5 from the waste sector in Accra, a change from the business-as-usual to more sustainable options would reduce air pollutants emissions and avert 120 premature deaths in 2030. Levels of air pollution in Accra are significant and interventions to reduce PM2.5 exposure should be promoted. The detailed analysis of the current situation provides suggestions for waste management policies in terms of impacts on health and ideas to reconsider the waste policies in Accra.

Source sector and fuel contributions to ambient PM2.5 and attributable mortality across multiple spatial scales.

Ambient fine particulate matter (PM2.5) is the world's leading environmental health risk factor. Reducing the PM2.5 disease burden requires specific strategies that target dominant sources across multiple spatial scales. We provide a contemporary and comprehensive evaluation of sector- and fuel-specific contributions to this disease burden across 21 regions, 204 countries, and 200 sub-national areas by integrating 24 global atmospheric chemistry-transport model sensitivity simulations, high-resolution satellite-derived PM2.5 exposure estimates, and disease-specific concentration response relationships. Globally, 1.05 (95% Confidence Interval: 0.74-1.36) million deaths were avoidable in 2017 by eliminating fossil-fuel combustion (27.3% of the total PM2.5 burden), with coal contributing to over half. Other dominant global sources included residential (0.74 [0.52-0.95] million deaths; 19.2%), industrial (0.45 [0.32-0.58] million deaths; 11.7%), and energy (0.39 [0.28-0.51] million deaths; 10.2%) sectors. Our results show that regions with large anthropogenic contributions generally had the highest attributable deaths, suggesting substantial health benefits from replacing traditional energy sources.

Distal radius strength: a comparison of DXA-derived vs pQCT-measured parameters in adolescent females.

Although quantitative computed tomography (QCT) is considered the gold standard for in vivo densitometry, dual-energy X-ray absorptiometry (DXA) scans assess larger bone regions and are more appropriate for pediatric longitudinal studies. Unfortunately, DXA does not yield specific bone architectural output. To address this issue in healthy, postmenarcheal girls, Sievänen's distal radius formulae [1996] were applied to derive indices of bone geometry, volumetric bone mineral density (vBMD), and strength from DXA data; results were compared to peripheral quantitative computed tomography (pQCT) output. Contemporaneous scans were performed on the left, distal radii of 35 gymnasts, ex-gymnasts, and nongymnasts (aged 13.3-20.4 yr, mean 16.6 yr). For 4% and 33% regions, pQCT measured cross-sectional areas (CSAs) and vBMD; comparable DXA indices were generated at ultradistal and 1/3 regions. Index of structural strength in axial compression was calculated from 4% pQCT and DXA output for comparison; 33% pQCT strength-strain index was compared to 1/3 DXA section modulus. Sievänen DXA indices were significantly, positively correlated with pQCT output (R=+0.61 to +0.98; p<0.0001). At the distal radius, in healthy postmenarcheal girls, Sievänen's method yielded potentially useful DXA indices of diaphyseal cortical CSA and bone strength at both the diaphysis (section modulus) and the metaphysis (index of structural strength in axial compression).

Histomorphometric evidence of growth plate recovery potential after fractionated radiotherapy: an in vivo model.

This study evaluated the hypothesis that early growth plate radiorecovery is evident by growth rate, histomorphometric and immunohistochemical end points after exposure to clinically relevant fractionated radiation in vivo. Twenty-four weanling 5-week-old male Sprague-Dawley rats were randomized into eight groups. In each animal, the right distal femur and proximal tibia were exposed to five daily fractions of 3.5 Gy (17.5 Gy) with the left leg serving as a control. Rats were killed humanely at 7, 8, 9, 10, 11, 14, 15 and 16 days after the first day of radiation exposure. Quantitative end points calculated included individual zonal and overall growth plate heights, area matrix fraction, OTC-labeled growth rate, chondrocyte clone volume and numeric density, and BrdU immunohistochemical labeling for proliferative index. Transient postirradiation reductions occurred early and improved during observation for growth rate, proliferative indices, transitional/hypertrophic zone matrix area fraction, proliferative height, and clonal volume. Reserve and hypertrophic zone height remained increased during the period of observation. The current model, using a more clinically relevant fractionation scheme than used previously, shows early evidence of growth plate recovery and provides a model that can be used to correlate temporal changes in RNA and protein expression during the early period of growth plate recovery.

Global health impacts and costs due to mercury emissions.

Since much of the emission is in the form of metallic Hg whose atmospheric residence time is long enough to cause nearly uniform mixing in the hemisphere, much of the impact is global. This article presents a first estimate of global average neurotoxic impacts and costs by defining a comprehensive transfer factor for ingestion of methyl-Hg as ratio of global average dose rate and global emission rate. For the dose-response function (DRF) we use recent estimates of IQ decrement as function of Hg concentration in blood, as well as correlations between blood concentration and Hg ingestion. The cost of an IQ point is taken as $18,000 in the United States and applied in other countries in proportion to per capita GDP, adjusted for purchase power parity. The mean estimate of the global average of the marginal damage cost per emitted kg of Hg is about $1,500/kg, if one assumes a dose threshold of 6.7 mug/day of methyl-Hg per person, and $3,400/kg without threshold. The average global lifetime impact and cost per person at current emission levels are 0.02 IQ points lost and $78 with and 0.087 IQ points and $344 without threshold. These results are global averages; for any particular source and emission site the impacts can be quite different. An assessment of the overall uncertainties indicates that the damage cost could be a factor 4 smaller or larger than the median estimate (the uncertainty distribution is approximately log normal and the ratio median/mean is approximately 0.4).

Air quality co-benefits for human health and agriculture counterbalance costs to meet Paris Agreement pledges.

Local air quality co-benefits can provide complementary support for ambitious climate action and can enable progress on related Sustainable Development Goals. Here we show that the transformation of the energy system implied by the emission reduction pledges brought forward in the context of the Paris Agreement on climate change (Nationally Determined Contributions or NDCs) substantially reduces local air pollution across the globe. The NDCs could avoid between 71 and 99 thousand premature deaths annually in 2030 compared to a reference case, depending on the stringency of direct air pollution controls. A more ambitious 2 °C-compatible pathway raises the number of avoided premature deaths from air pollution to 178-346 thousand annually in 2030, and up to 0.7-1.5 million in the year 2050. Air quality co-benefits on morbidity, mortality, and agriculture could globally offset the costs of climate policy. An integrated policy perspective is needed to maximise benefits for climate and health.

Health Impacts and Economic Costs of Air Pollution in the Metropolitan Area of Skopje.

BACKGROUND: Urban outdoor air pollution, especially particulate matter, remains a major environmental health problem in Skopje, the capital of the former Yugoslav Republic of Macedonia. Despite the documented high levels of pollution in the city, the published evidence on its health impacts is as yet scarce. METHODS: we obtained, cleaned, and validated Particulate Matter (PM) concentration data from five air quality monitoring stations in the Skopje metropolitan area, applied relevant concentration-response functions, and evaluated health impacts against two theoretical policy scenarios. We then calculated the burden of disease attributable to PM and calculated the societal cost due to attributable mortality. RESULTS: In 2012, long-term exposure to PM2.5 (49.2 µg/m³) caused an estimated 1199 premature deaths (CI95% 821-1519). The social cost of the predicted premature mortality in 2012 due to air pollution was estimated at between 570 and 1470 million euros. Moreover, PM2.5 was also estimated to be responsible for 547 hospital admissions (CI95% 104-977) from cardiovascular diseases, and 937 admissions (CI95% 937-1869) for respiratory disease that year. Reducing PM2.5 levels to the EU limit (25 µg/m³) could have averted an estimated 45% of PM-attributable mortality, while achieving the WHO Air Quality Guidelines (10 µg/m³) could have averted an estimated 77% of PM-attributable mortality. Both scenarios would also attain significant reductions in attributable respiratory and cardiovascular hospital admissions. CONCLUSIONS: Besides its health impacts in terms of increased premature mortality and hospitalizations, air pollution entails significant economic costs to the population of Skopje. Reductions in PM2.5 concentrations could provide substantial health and economic gains to the city.

Connective tissue growth factor and insulin-like growth factor 2 show upregulation in early growth plate radiorecovery response following irradiation.

INTRODUCTION: The growth plate response following radiotherapy is poorly understood. In particular, little is known about the changes in growth plate growth factors and cytokines following irradiation. The hypothesis was that a limited number of growth factors and cytokines play a role in growth plate proliferative and hypertrophic chondrocyte radio-recovery. METHODS: The right limbs of 6 rats were irradiated (17.5 Gy), leaving the left limbs as controls. Limbs were harvested 1 (n = 3) and 2 (n = 3) weeks later. Microarrays were constructed from chondrocytes obtained by laser microdissection from the proliferative zone (PZ) and the hypertrophic zone (HZ) of normal and irradiated tibia growth plates. Real-time PCR was used to confirm the expression of parathyroid hormone receptor 1 (Pthr1), connective tissue growth factor (CTGF), insulin-like growth factor I receptor (IGF1R), insulin-like growth factor II (IGF2), interleukin 17beta (IL17b) and chemokine ligand 12 (CXCL12). RESULTS AND CONCLUSIONS: IGF2 is upregulated in the PZ and CTGF is upregulated in both the PZ and HZ 1 week after irradiation, prior to the histomorphometric appearance of growth plate recovery in this immature animal radiation model, supporting their role in stimulating early return of the growth plate. By 2 weeks after irradiation, a number of growth factors and cytokines, including CTGF and Pthr1 in both zones, CXCL12 and its receptor in the PZ, and IL17b and bone morphogenetic protein 2 in the HZ, show upregulation, suggesting a possible later role in radiorecovery. The effects of irradiation on Pthr1, CTGF, IGF2 and CXCL12 in PZ and Pthr1, CTGF, IL17b and IGF1R in the HZ determined by microarray and real-time RT-PCR was highly correlated (r = 0.797, p < 0.05 in the PZ and r = 0.875, p < 0.01 in the HZ, respectively).