Low Threshold Concentrations Research Articles

Blood: a very special juice. The good and the evil

In Goethe’s Faust, Mephistopheles stated, ‘Blood is a juice of very special kind.’ As illustrated in this famous German folklore, blood is the essence of life but it can also lead to the destruction of life if improperly used. The human heart constantly pumps on average between 5 and 6 l of blood throughout the body to maintain the supply of nutrients and oxygen to organs and cells, which is essential for life. Indeed, Mephistopheles was correct in his observation that when we start to talk about blood, we are talking about something very special. The question to initiate red blood cells (RBCs) transfusion is a daily clinical decision in the operating theatre, as the most secure strategy for managing patients with low haemoglobin has not yet been properly established. Moreover, the definition of low haemoglobin concentration thresholds remains controversial [1]. It is with certainty that markers are needed to help clinicians identify whether a patient would benefit from blood transfusion. This remains a relevant research topic and is in line with the fact that we definitely have a lot to learn about erythrocyte transfusion. Willems et al. [2] investigated this important issue in a large retrospective study, looking at the outcome of children after cardiac surgery. They hypothesized that the timing of blood transfusion plays a key role in the difference in patient outcomes. The conclusion of the study showed that transfusions administered therapeutically were associated with increased morbidity and mortality, compared with transfusions administered simply to avoid a low haematocrit during cardiopulmonary bypass (CPB). On the other hand, higher preoperative weight was associated with a lower risk of severe postoperative morbidity or mortality. The important finding of this study was that it is the reason for transfusion rather than the transfusion itself that increased the perioperative risk. Although an association between erythrocyte transfusion and increased perioperative mortality is usually observed, unmeasured confounding factors may also excessively influence this association. One of these unmeasured confounding factors might be the indication for transfusion and might, therefore, directly influence increased perioperative morbidity and mortality itself.

Amphiphilic O-functionalized calix[4]resocinarenes with tunable structural behavior

Novel amphiphilic calix[4]resorcinarenes oxyethylated at the upper rim and alkylated at the lower rim (CR–CnH2n+1, here n is the number of carbon atoms in the alkyl substituent; n = 2,5,7,8,9,11) were synthesized, and their association behavior in water-organic solvents was explored. Surface properties and the association behavior of CRs were shown to be strongly controlled by their structure and the nature of the co-solvent. Solely CR–C5H11 demonstrates surface activity in the mixed water–DMF and water–DMSO solutions, while no surface activity occurs in the water–THF mixture. The DLS measurements revealed a very low concentration threshold of the aggregation (around 0.01 mM) for the CR series including surface inactive compounds. In water–DMF and water–DMSO solutions the CRs of low hydrophobicity were shown to associate through an open model with the formation of large aggregates of 300–400 nm, while more hydrophobic CRs can associate through a closed model and form rather small micelle-like aggregates of 10 to 20 nm.

Upper and Lower Concentration Thresholds for Bulk Organic Substrates in Bioremediation of Acid Mine Drainage

Acidic pit lakes can form in open cut mine voids that extend below the groundwater table. The aim of this research was to determine what bulk organic material concentrations best stimulated sulphate-reducing bacteria (SRB) for acid mine drainage (AMD) treatment within a pit lake. An experiment was carried out to assess the effect of different substrate concentrations of sewage sludge on AMD bioremediation efficiency. Experimental microcosms were made of 300 mm long and 100 mm wide acrylic cores, with a total volume of 1.8 L. Four different concentrations of sewage sludge (ranging from 30 to 120 g/L) were tested. As the sewage sludge concentration increased, the bioremediation efficiency also increased, reflecting the higher organic carbon concentrations. Sewage sludge contributed alkaline materials that directly neutralised the AMD in proportion to the quantity added and therefore played a primary role in stimulating SRB bioremediation. The lowest concentration of sewage sludge (30 g/L) tested proved to be inadequate for effective SRB bioremediation. However, there were no measurable beneficial effects on SRB bioremediation efficiency when sewage sludge was added at concentrations >60 g/L. We compared our results with existing literature data to develop a conceptual model for remediation of AMD in pit lakes through organic material amendments. The model indicated that labile organic carbon availability was more important to the bioremediation rate than AMD strength, so long as iron and sulphate concentrations were not limiting. The conceptual model also indicates that bioremediation may still occur when only low concentrations of organic carbon are present in the pit lakes, albeit at a very slow rate. The model also demonstrates the presence of an organic material amendment threshold where excess organic carbon does not measurably influence the final outcome. The conceptual model defined is well supported by the results of the microcosm experiment.

Tunable biomimetic systems based on a novel amphiphilic pyrimidinophane and a helper nonionic surfactant

Tunable nanosystems based on a novel water insoluble pyrimidinic amphiphile are designed. pH dependent aggregates composed of protonated pyrimidinophane 1 are formed at pH<4, which undergo reversible transition to precipitate at neutral and basic conditions. The approach assuming the application of a helper nonionic surfactant Triton-X-100 (TX-100) is used in this work. Different models of a self-assembly were found depending on the molar ratio of components and solution pH. In the equimolar 1−TX-100 solution, mixed assemblies contributed by aggregated molecules of both TX-100 and cationic form of 1 are formed in acidic conditions. Upon alkalization, deprotonated pyrimidinophane molecules shift toward the micellar core. The assemblies undergo reversible precipitation after 4–5h, while the excess of TX-100 leads to the formation of highly stable mixed aggregates. The acidification–alkalization cycles followed by the aggregation/precipitation and the re-charging of aggregates can be multiply repeated. Surprisingly, stable mixed aggregates are also formed under the excess of pyrimidinophane in both the acidic and alkaline conditions, but at a certain component ratio. They are characterized by the highest micellization degree among all the systems studied. The low concentration threshold of these assemblies in alkali solution is probably due to their nonionic character.

The effect of grid resolution on estimates of the burden of ozone and fine particulate matter on premature mortality in the United States.

Assessments of human health impacts associated with outdoor air pollution often use air quality models to represent exposure, but involve uncertainties due to coarse model resolution. Here we quantify how estimates of mortality in the United States attributable to ozone (O3) and fine particulate matter (PM2.5) at coarse resolution differ from those at finer resolution. Using the finest modeled concentrations (12 km), we estimate that 66,000 (95% CI, 39,300 - 84,500) all-cause and 21,400 (5,600 - 34,200) respiratory deaths per year are attributable to PM2.5 and O3 concentrations above low-concentration thresholds, respectively. Using model results at 36 km resolution gives mortality burdens that are 11% higher for PM2.5 and 12% higher for O3 than the 12 km estimates, suggesting a modest positive bias. We also scale modeled concentrations at 12 km to coarser resolutions by simple averaging, and repeat the mortality assessment at multiple resolutions from 24 to 408 km, including the resolutions of global models; in doing so, we account for the effect of resolution on population exposure. Coarse grid resolutions produce mortality estimates that are substantially biased low for PM2.5 (30-40% lower than the 12 km estimate at >250 km resolution), but less than 6% higher for O3 at any resolution. Mortality estimates for primary PM2.5 species show greater bias at coarse resolution than secondary species. These results suggest that coarse resolution global models (>100 km) are likely biased low for PM2.5 health effects. For ozone, biases due to coarse resolution may be much smaller, and the effect on modeled chemistry likely dominates.

Investigating the Mechanism of Action of Antimicrobial Piscidin in Bacterial and Mammalian Lipid Membrane Mimics using Oriented Circular Dichroism

Antimicrobial peptides (AMPs) are a class of amphiphilic, often cationic peptides, which are able to target and permeabilize the lipid membranes of pathogenic microbes. AMPs are often studied for their potential as novel pharmaceuticals against bacteria, viruses, and even some cancers. Many possible mechanisms for their action have been proposed, but it is believed that at low peptide:lipid ratios (P/L), peptides bind parallel to the membrane surface, known as the “S-state,” while at high P/L, peptides insert into the membrane and bind in the “I-state” perpendicular to the membrane surface. It is proposed that peptides in the I-state form pores, while peptides that remain in the S-state use the carpet model of membrane disruption.Here, OCD is used to investigate the orientation and threshold concentration of Piscidin 1 and Piscidin 3 (P3) in bacterial and mammalian-mimicking lipid systems and thereby determine the mechanism of action of P1 and P3 in these lipid systems. Both peptides are a 22-residue alpha-helical AMPs isolated from the mast cells of hybrid striped sea bass. P1 is both more antimicrobial and hemolytic than P3. We hypothesize that the two peptides behave differently in bacterial versus human cells due to the differences in membrane composition and that P1 initiates its activity at a lower threshold concentration. Mammalian and bacterial membrane mimics have been made using 4:1 PC/CHL (phosphocholine and cholesterol, respectively) and 3:1 PC/PG (phosphoglycerol). The bilayer orientations of piscidin have been investigated over a large range of P/L ratios using OCD. Membrane thinning was studied by x-ray. These studies provide insight into the mechanism of action of an important class of AMPs and may help provide design principles for new drug candidates.

Orthogonal Design Study on Factors Affecting the Determination of Common Odors in Water Samples by Headspace Solid-Phase Microextraction Coupled to GC/MS

Geosmin and 2-MIB are responsible for the majority of earthy and musty events related to the drinking water. These two odorants have extremely low odor threshold concentrations at ng L−1 level in the water, so a simple and sensitive method for the analysis of such trace levels was developed by headspace solid-phase microextraction coupled to gas chromatography/mass spectrometry. In this study, the orthogonal experiment design L32 (49) was applied to arrange and optimize experimental conditions. The optimum was the following: temperatures of extraction and desorption, 65°C and 260°C, respectively; times of extraction and desorption, 30 min and 5 min, respectively; ionic strength, 25% (w/v); rotate-speed, 600 rpm; solution pH, 5.0. Under the optimized conditions, limits of detection (S/N = 3) were 0.04 and 0.13 ng L−1 for geosmin and 2-MIB, respectively. Calculated calibration curves gave high levels of linearity with a correlation coefficient value of 0.9999 for them. Finally, the proposed method was applied to water samples, which were previously analyzed and confirmed to be free of target analytes. Besides, the proposal method was applied to test environmental water samples. The RSDs were 2.75%~3.80% and 4.35%~7.6% for geosmin and 2-MIB, respectively, and the recoveries were 91%~107% and 91%~104% for geosmin and 2-MIB, respectively.

Asthmatic Airway Neutrophilia after Allergen Challenge Is Associated with the Glutathione S-Transferase M1 Genotype

Asthma is a heterogeneous lung disorder characterized by airway inflammation and airway dysfunction, manifesting as hyperresponsiveness and obstruction. Glutathione S-transferase M1 (GSTM1) is a multifunctional phase II enzyme and regulator of stress-activated cellular signaling relevant to asthma pathobiology. A common homozygous deletion polymorphism of the GSTM1 gene eliminates enzyme activity. To determine the effect of GSTM1 on airway inflammation and reactivity in adults with established atopic asthma in vivo. Nineteen GSTM1 wild-type and eighteen GSTM1-null individuals with mild atopic asthma underwent methacholine and inhaled allergen challenges, and endobronchial allergen provocations through a bronchoscope. The influx of inflammatory cells, panels of cytokines and chemokines linked to asthmatic inflammation, F(2)-isoprostanes (markers of oxidative stress), and IgE were measured in bronchoalveolar lavage fluid at baseline and 24 hours after allergen instillation. Individuals with asthma with the GSTM1 wild-type genotype had greater baseline and allergen-provoked airway neutrophilia and concentrations of myeloperoxidase than GSTM1-null patients. In contrast, the eosinophilic inflammation was unaffected by GSTM1. The allergen-stimulated generation of acute-stress and proneutrophilic mediators, tumor necrosis factor-α, CXCL-8, IL-1β, and IL-6, was also greater in the GSTM1 wild-type patients. Moreover, post-allergen airway concentrations of IgE and neutrophil-generated mediators, matrix metalloproteinase-9, B-cell activating factor, transforming growth factor-β1, and elastase were higher in GSTM1 wild-type individuals with asthma. Total airway IgE correlated with B-cell activating factor concentrations. In contrast, levels of F(2)-isoprostane were comparable in both groups. Finally, GSTM1 wild-type individuals with asthma required lower threshold concentrations of allergen to produce bronchoconstriction. The functional GSTM1 genotype promotes neutrophilic airway inflammation in humans with atopic asthma in vivo.

Dose-dependence of antiapoptotic and toxic action of ouabain in neurons of primary cultures of rat cortex

Effects of 0.01 nM–1 nM ouabain on neuronal survival in excitotoxic stress and ouabain self toxic action in concentrations from 10 nM to 30 μM were studied. Neuronal viability was evaluated by measuring Bcl-2 protein expression and using vital staining test allowing recognition of live, necrotic and apoptotic cells. Excitotoxic stress was induced by 240-min treatment with agonists of ionotropic glutamate receptors (NMDA or kainate). Experiments were performed on rat primary neuronal cultures of 7–14 DIV (days in vitro). Thirty μM NMDA induced apoptosis in 45 ± 9% (n = 5), and 30 μM kainate, in 52 ± 5% (n = 5) of neurons. An antiapoptotic effect of ultra low (0.01 nM–1 nM) ouabain concentrations was found to restore Bcl-2 expression and to bring apoptosis level back to control values (about 10%, n = 5). Since in this concentration range ouabain is not able to inhibit NKA, we conclude that neuroprotection discloses the signaling function of NKA. Whereas ouabain self toxic action in higher concentrations (10 nM–30 μM, during 240 min) resulted in necrotic death of 45% neurons (apoptosis remained as under the control conditions), the large portion of neurons were unaffected. The relatively low threshold concentration of ouabain toxic action (10 nM) is consistent with the sensitivity to ouabain of α3-isoform of NKA. Thus, ouabain was found to have a bimodal effect, including antiapoptotic action in excitotoxic stress in the concentration range from 0.01 nM to 1 nM, and self toxic action at larger concentrations. Self toxicity of ouabain is initiated through inhibition of NKA pumping function. Neuronal heterogeneity with respect to ouabain toxic action is probably related with the different expression of α1 and α3-isoforms of NKA in pyramid neurons and interneurons.

Influence of chemical structure on absolute odour thresholds and odour characteristics of ortho‐ and para‐halogenated phenols and cresols

ABSTRACTHalogenated phenols and cresols belong to a group of volatiles consistently reported as off‐flavour compounds. For example, 2‐iodophenol and 2‐iodo‐4‐methylphenol with their typical medicinal smell were found to negatively affect bottled mineral water. Even though these compounds are widespread in nature no comprehensive information about their chemo‐analytical as well as odour properties is available. Therefore, the objective of this study were (1) to provide systematic chemo‐analytical data on these substances, such as mass spectral data and retention parameters in gas chromatographic analysis, and (2) to determine, on a direct comparative basis, the sensory properties of eight mono‐halogenated phenols, four di‐halogenated phenols and four halogenated cresols. Evaluations focused on the determination of odour quality and odour threshold concentration in air and water. With regard to the relationship between substitution pattern and odour character, the location of an iodine atom in the ortho‐position was demonstrated to obviously be an important prerequisite for medicinal, plaster‐like or ink‐like smell. Faecal or horse stable‐like odour notes were predominantly related to compounds being substituted either by halogen moieties or by a methyl group in the para‐position. The 2‐halogenated 4‐methylphenols were found to be the odorants with the lowest odour threshold concentrations of all the compounds investigated in this study, and that, generally, compounds with ortho‐halogenation exhibited exceptionally low odour threshold concentrations. Copyright © 2012 John Wiley &amp; Sons, Ltd.

Low versus high haemoglobin concentration threshold for blood transfusion for preventing morbidity and mortality in very low birth weight infants

Infants of very low birth weight often receive multiple transfusions of red blood cells, usually in response to predetermined haemoglobin or haematocrit thresholds. In the absence of better indices, haemoglobin levels are imperfect but necessary guides to the need for transfusion. Chronic anaemia in premature infants may, if severe, cause apnoea, poor neurodevelopmental outcomes or poor weight gain.On the other hand, red blood cell transfusion may result in transmission of infections, circulatory or iron overload, or dysfunctional oxygen carriage and delivery. To determine if erythrocyte transfusion administered to maintain low as compared to high haemoglobin thresholds reduces mortality or morbidity in very low birth weight infants enrolled within three days of birth. Two review authors independently searched the Cochrane Central Register of Controlled Trials (The Cochrane Library) , MEDLINE,EMBASE, and conference proceedings through June 2010. We selected randomised controlled trials (RCTs) comparing the effects of early versus late, or restrictive versus liberal erythrocyte transfusion regimes in low birth weight infants applied within three days of birth, with mortality or major morbidity as outcomes.

Wind Tunnel Experiment of Tracer Gas Concentration Fluctuation in Turbulent Boundary Layer Characteristics of Concentration Fluctuation with Low Concentration Threshold

Wind Tunnel Experiment of Tracer Gas Concentration Fluctuation in Turbulent Boundary Layer Characteristics of Concentration Fluctuation with Low Concentration Threshold

Induced Terpene Accumulation in Norway Spruce Inhibits Bark Beetle Colonization in a Dose-Dependent Manner

BackgroundTree-killing bark beetles (Coleoptera, Scolytinae) are among the most economically and ecologically important forest pests in the northern hemisphere. Induction of terpenoid-based oleoresin has long been considered important in conifer defense against bark beetles, but it has been difficult to demonstrate a direct correlation between terpene levels and resistance to bark beetle colonization.MethodsTo test for inhibitory effects of induced terpenes on colonization by the spruce bark beetle Ips typographus (L.) we inoculated 20 mature Norway spruce Picea abies (L.) Karsten trees with a virulent fungus associated with the beetle, Ceratocystis polonica (Siem.) C. Moreau, and investigated induced terpene levels and beetle colonization in the bark.ResultsFungal inoculation induced very strong and highly variable terpene accumulation 35 days after inoculation. Trees with high induced terpene levels (n = 7) had only 4.9% as many beetle attacks (5.1 vs. 103.5 attacks m−2) and 2.6% as much gallery length (0.029 m m−2 vs. 1.11 m m−2) as trees with low terpene levels (n = 6). There was a highly significant rank correlation between terpene levels at day 35 and beetle colonization in individual trees. The relationship between induced terpene levels and beetle colonization was not linear but thresholded: above a low threshold concentration of ∼100 mg terpene g−1 dry phloem trees suffered only moderate beetle colonization, and above a high threshold of ∼200 mg terpene g−1 dry phloem trees were virtually unattacked.Conclusion/SignificanceThis is the first study demonstrating a dose-dependent relationship between induced terpenes and tree resistance to bark beetle colonization under field conditions, indicating that terpene induction may be instrumental in tree resistance. This knowledge could be useful for developing management strategies that decrease the impact of tree-killing bark beetles.

On Electrospinning of PFSA: A Comparison between Long and Short-Side Chain Ionomers

Long- and short-side chain perfluorosulfonic acid polymers have been electrospun into nonwoven nanofibre membranes. The membranes show homogeneous nanofibrous morphology, with the short-side chain showing narrower fibre size distribution and thinner fibre dimension due to lower threshold concentration of carrier polymer for fibre formation. The electrospun membranes show comparable proton conductivity to cast membranes.

Nhe1 Is Essential for Potassium but Not Calcium Facilitation of Cell Motility and the Monovalent Cation Requirement for Chemotactic Orientation in Dictyostelium discoideum

In Dictyostelium discoideum, extracellular K+ or Ca2+ at a concentration of 40 or 20 mM, respectively, facilitates motility in the absence or presence of a spatial gradient of chemoattractant. Facilitation results in maximum velocity, cellular elongation, persistent translocation, suppression of lateral pseudopod formation, and myosin II localization in the posterior cortex. A lower threshold concentration of 15 mM K+ or Na or 5 mM Ca2+ is required for chemotactic orientation. Although the common buffer solutions used by D. discoideum researchers to study chemotaxis contain sufficient concentrations of cations for chemotactic orientation, the majority contain insufficient levels to facilitate motility. Here it has been demonstrated that Nhe1, a plasma membrane protein, is required for K+ but not Ca2+ facilitation of cell motility and for the lower K+ but not Ca2+ requirement for chemotactic orientation.

Application of algae in biomonitoring and phytoextraction of heavy metals contamination in urban stream water

Biological technologies for wastewater remediation techniques employed to remove contaminants in urban stream water are increasingly receiving attention worldwide. The purpose of this study was therefore to determine the concentrations of lead, cadmium, copper, zinc, manganese and iron in algal biomass and establish the feasibility of using algae in phytoextraction and bio-monitoring of environmental quality. Analysis of algal biomass samples in the Nakivubo urban stream ecosystem, Kampala, Uganda, showed that there was contamination by lead, cadmium, copper and zinc as indicated by enrichment factor and pollution load index values. It is suspected that industrial and vehicular emissions are the major sources of these pollutants. Calculated bio-concentration factor was >- 1000 but with low concentration thresholds in each element, suggesting that algal biomass was a very good heavy metal accumulator. The bio-concentration values in algal biomass were found to be in the order of copper > zinc > lead > cadmium in the Nakivubo Channelized stream. In conclusion, algae can be a promising aquatic bio-filter plant for phytoextraction and bio-monitoring of polluted urban stream ecosystems and wastewater.

Interactions between limiting nutrients: Consequences for somatic and population growth of Daphnia magna

To assess the significance of nutrient interactions on animal performance, life‐history experiments were conducted with the freshwater herbivore Daphnia magna in a system with two limiting nutrients (i.e., sterols and polyunsaturated fatty acids [PUFAs]). By experimentally increasing the availability of dietary cholesterol either in the absence or in the presence of different dietary PUFAs we investigated whether dietary PUFAs differ in their potential to affect the sterol‐limited growth kinetics of the herbivore. Sterol‐limited growth responses of D. magna were characterized by a higher initial slope of the saturation curves and lower threshold concentrations in the presence of dietary PUFAs. This suggests significant interactions between limiting nutrients and lower dietary sterol requirements in the presence of dietary PUFAs. In contrast to somatic growth rates, which were significantly increased only by additional supplementation with eicosapentaenoic acid (EPA), population growth rates were significantly affected by additional supplementation with linoleic acid, α‐linolenic acid, docosahexaenoic acid (DHA), and in particular EPA and arachidonic acid. The fatty acid composition of D. magna reflected that of their diet. However, animals fed the DHA supplemented diet contained considerable amounts of EPA, indicating a retro‐conversion of DHA into EPA within their metabolism. The fitness of resource‐limited consumers is strongly affected by complex interactions between limiting nutrients and this topic has to be considered in experimental and theoretical studies investigating nutrient‐limited growth responses of animals to accurately assess consequences for population dynamics.

Effects of pentanol isomers on the phase behavior of phospholipid bilayer membranes

Differential scanning calorimetry (DSC) was used to analyze the thermotropic phase behavior of dipalmitoylphosphatidylcholine (DPPC) bilayers in the presence of pentanol isomers. The concentration of each pentanol isomer needed to induce the interdigitated phase was determined by the appearance of a biphasic effect in the main transition temperatures, the onset of a hysteresis associated with the main transition from the gel-to-liquid crystalline phase, and the disappearance of the pretransition. Lower threshold concentrations were found to correlate with isomers of greater alkyl chain length while branching of the alkyl chain was found to increase biphasic behavior. The addition of a methyl group to butanol systems drastically decreased threshold concentrations. However, as demonstrated in the DPPC/neopentanol system, branching of the alkyl chain away from the –OH group lowers the threshold concentration while maintaining a biphasic effect.

Matrix-Calibrated LC-MS/MS Quantitation and Sensory Evaluation of Oak Ellagitannins and Their Transformation Products in Red Wines

Aimed at investigating the concentrations and taste contribution of the oak-derived ellagitannins castalagin and vescalagin as well as their transformation products acutissimin A/B, epiacutissimin A/B, and beta-1-O-ethylvescalagin in red wine, a highly sensitive and accurate quantification method was developed on the basis of LC-MS/MS-MRM analysis with matrix calibration. Method validation showed good recovery rates ranging from 102.4 +/- 5.9% (vescalagin) to 113.7 +/- 15.2% (epiacutissimin A). In oak-matured wines, castalagin was found as the predominant ellagitannin, followed by beta-1-O-ethylvescalagin, whereas the flavano-C-ellagitannins (epi)acutissimin A/B were present in significantly lower amounts. In contrast to the high threshold concentration levels (600-1000 micromol/L) and the puckering astringent orosensation induced by flavan-3-ols, all of the ellagitannin derivatives were found to induce a smooth and velvety astringent oral sensation at rather low threshold concentrations ranging from 0.9 to 2.8 micromol/L. Dose/activity considerations demonstrated that, among all the ellagitannins investigated, castalagin exclusively exceeded its threshold concentration in various oak-matured wine samples.

An Estimate of the Global Burden of Anthropogenic Ozone and Fine Particulate Matter on Premature Human Mortality Using Atmospheric Modeling

BackgroundGround-level concentrations of ozone (O3) and fine particulate matter [≤ 2.5 μm in aerodynamic diameter (PM2.5)] have increased since preindustrial times in urban and rural regions and are associated with cardiovascular and respiratory mortality.ObjectivesWe estimated the global burden of mortality due to O3 and PM2.5 from anthropogenic emissions using global atmospheric chemical transport model simulations of preindustrial and present-day (2000) concentrations to derive exposure estimates.MethodsAttributable mortalities were estimated using health impact functions based on long-term relative risk estimates for O3 and PM2.5 from the epidemiology literature. Using simulated concentrations rather than previous methods based on measurements allows the inclusion of rural areas where measurements are often unavailable and avoids making assumptions for background air pollution.ResultsAnthropogenic O3 was associated with an estimated 0.7 ± 0.3 million respiratory mortalities (6.3 ± 3.0 million years of life lost) annually. Anthropogenic PM2.5 was associated with 3.5 ± 0.9 million cardiopulmonary and 220,000 ± 80,000 lung cancer mortalities (30 ± 7.6 million years of life lost) annually. Mortality estimates were reduced approximately 30% when we assumed low-concentration thresholds of 33.3 ppb for O3 and 5.8 μg/m3 for PM2.5. These estimates were sensitive to concentration thresholds and concentration–mortality relationships, often by > 50%.ConclusionsAnthropogenic O3 and PM2.5 contribute substantially to global premature mortality. PM2.5 mortality estimates are about 50% higher than previous measurement-based estimates based on common assumptions, mainly because of methodologic differences. Specifically, we included rural populations, suggesting higher estimates; however, the coarse resolution of the global atmospheric model may underestimate urban PM2.5 exposures.