Outcomes of Local Radiation and Intensified Combined Intrathecal Methotrexate and High-dose Chemotherapy for Intracranial Germ Cell Tumors.

Many attempts to reduce radiation fields for intracranial germ cell tumors (iGCTs) remain unsuccessful. To assess the possibility of reduction, we analyzed registry data of 57 patients who mostly underwent local irradiation for iGCTs between 1997 and 2006. The recommended treatment for pure germinomas (PGNs) included 3 courses of cisplatin and etoposide followed by 24 Gy local irradiation. Intensified chemotherapy using a combination of cyclophosphamide and intrathecal methotrexate was recommended for human chorionic gonadotropin-producing germinomas (hCG-GNs) and nongerminomatous germ cell tumors (NGGCTs); both received 50.4 Gy local irradiation. High-dose chemotherapy was only administered for residual NGGCTs after chemoradiotherapy. Craniospinal irradiation was recommended only in metastatic cases. During the median follow-up of 114.8 months, 8 of 9 relapses from 24 PGNs occurred outside irradiation fields, with a 5-year progression-free survival (5-year PFS) of 75%±8.8%. Conversely, no recurrences occurred from 11 hCG-GNs, with a 5-year PFS of 100%. Eleven of 22 patients with NGGCTs received high-dose chemotherapy; the 5-year PFS was 81.3%±8.4%; 2 of 3 relapses occurred in the spinal cord. Thus, local irradiation for PGNs was insufficient without treatment intensification. The introduction of intensified chemotherapy improved outcomes of both patients with hCG-GNs and NGGCTs. However, the contributions of either modality remained unclear.

Endoscopic third ventriculostomy for hydrocephalus in osteopetrosis: a case report and review of the literature.

INTRODUCTION: There are very few reports in the literature associating in hydrocephalus in osteopetrosis. As a complication of shunt procedure, there are two reports on shunt malfunction due to osseous overgrowth at the burr hole in patients with osteopetrosis. We herein report a case of osteopetrosis with hydrocephalus that was successfully treated with endoscopic third ventriculostomy (ETV). CASE REPORT: At 5 months of age, a male patient presented with developmental delay. Head computed tomography (CT) demonstrated triventricular hydrocephalus with a cerebellar tonsillar herniation. At 7 months of age, he underwent suboccipital decompression with decompression of the foramen magnum. The hydrocephalus did not improve postoperatively, and the patient was transferred to our hospital. At 12 months of age, the hydrocephalus was successfully treated with ETV. The postoperative period was uneventful. Postoperative CT demonstrated an improvement in the ventricle size. CONCLUSIONS: The etiology of hydrocephalus in osteopetrosis is not completely understood; however, there have been several reports in which ETV was effective. ETV should be considered the treatment of choice for hydrocephalus in osteopetrosis, as it avoids the characteristic shunt complications that can occur in patients with osteopetrosis.

Sensitivities of Simulated Source Contributions and Health Impacts of PM2.5 to Aerosol Models.

Chemical transport models are useful tools for evaluating source contributions and health impacts of PM2.5 in the atmosphere. We recently found that concentrations of PM2.5 compounds over Japan were much better reproduced by a volatility basis set model with an enhanced dry deposition velocity of HNO3 and NH3 compared with a two-product yield model. In this study, we evaluated the sensitivities to organic aerosol models of the simulated source contributions to PM2.5 concentrations and of PM2.5-related mortality. Overall, the simulated source contributions to PM2.5 were similar between the two models. However, because of the improvements associated with the volatility basis set model, the contributions of ammonia sources decreased, particularly in winter and spring, and contributions of biogenic and stationary evaporative sources increased in spring and summer. The improved model estimated that emission sources in Japan contributed 35%-48% of the PM2.5-related mortality in Japan. These values were higher than the domestic contributions to average PM2.5 concentrations in Japan (26%-33%) because the domestic contributions were higher in higher population areas. These results indicate that control of both domestic and foreign emissions is necessary to reduce health impacts due to PM2.5 in Japan.

The efficacy and safety of burr-hole craniotomy without continuous drainage for chronic subdural hematoma and subdural hygroma in children under 2 years of age.

PURPOSE: Various treatment modalities have been used in the management of chronic subdural hematoma and subdural hygroma (CSDH/SDHy) in children. However, few studies have examined burr-hole craniotomy without continuous drainage in such cases. Here, we retrospectively evaluated the efficacy and safety of burr-hole craniotomy without continuous drainage for CSDH/SDHy in children under 2 years old. We also aimed to determine the predictors of CSDH/SDHy recurrence. METHODS: We conducted a retrospective chart review of 25 children under 2 years old who underwent burr-hole craniotomy without continuous drainage for CSDH/SDHy at a pediatric teaching hospital over a 10-year period. We analyzed the relationship between CSDH/SDHy recurrence and factors such as abusive head trauma, laterality of CSDH/SDHy, and subdural fluid collection type (hematoma or hygroma). RESULTS: CSDH/SDHy recurred in 5 of the 25 patients (20 %), requiring a second operation at an average of 0.92 ± 1.12 months after the initial procedure. The mean follow-up period was 25.1 ± 28.6 months. There were no complications related to either operation. None of the assessed factors were statistically associated with recurrence. CONCLUSIONS: Burr-hole craniotomy without continuous drainage for CSDH/SDHy appears safe in children aged under 2 years and results in a relatively low recurrence rate. No predictors of CSDH/SDHy recurrence were identified. Advantages of this method include avoiding external subdural drainage-related complications. However, burr-hole drainage may be more effective for CSDH, which our data suggests is more likely to recur than SDHy, providing the procedure is performed with specific efforts to reduce complications.

Medulloblastoma with suprasellar solitary massive metastasis: Case report.

It is extremely rare for metastasised medulloblastoma to form a large tumour in the suprasellar region. We present a case of medulloblastoma with large suprasellar metastasis at initial presentation. A 3-year and 5-month-old boy presented with a 1-month history of vomiting and loss of appetite, and body weight. Computed tomography and magnetic resonance imaging revealed a 20 mm × 20 mm mass in the suprasellar region and a 30 mm × 30 mm mass in the fourth cerebral ventricle. We performed endoscopic biopsy of the suprasellar tumour, and subsequently totally removed the vermian tumour through a suboccipital craniotomy. The histopathological findings revealed that both the suprasellar and vermian tumours were classic type and non SHH/WNT type medulloblastoma. The postoperative course was uneventful. The patient showed complete remission after chemotherapy. The tumour in the suprasellar region was most likely metastatic from the vermis. Endoscopic biopsy of the tumour in the suprasellar region and total removal of the tumour in the vermis in a one-stage operation followed by intensive chemotherapy with reduced dose radiotherapy may provide a satisfactory outcome.

Projecting Fine Particulate Matter-Related Mortality in East China.

China is suffering from severe air pollution from fine particulate matter [≤ 2.5 µm in aerodynamic diameter (PM2.5)], especially East China. But its future trends and potential health impacts remain unclear. The study objectives were to project future trends of PM2.5 and its short-term effect on mortality in East China by 2030. First, daily changes in PM2.5 concentrations between 2005 and 2030 were projected under the "current legislation" scenario (CLE) and the "maximum technically feasible reduction" scenario (MFR). Then, they were linked to six population projections, two mortality rate projections, and PM2.5-mortality associations to estimate the changes in PM2.5-related mortality in East China between 2005 and 2030. Under the CLE scenario, the annual mean PM2.5 concentration was projected to decrease by 0.62 µg/m(3) in East China, which could cause up to 124,000 additional deaths, when considering the population growth. Under the MFR scenario, the annual mean PM2.5 concentration was projected to decrease by 20.41 µg/m(3) in East China. At least 230,000 deaths could be avoided by such a large reduction in PM2.5 concentration under MFR scenario, even after accounting for the population growth. Therefore, our results suggest that reducing PM2.5 concentration substantially in East China would benefit the public health. Otherwise, it may still remain as a great health risk in the future, especially when the population keeps growing.

Global air quality and climate.

Emissions of air pollutants and their precursors determine regional air quality and can alter climate. Climate change can perturb the long-range transport, chemical processing, and local meteorology that influence air pollution. We review the implications of projected changes in methane (CH(4)), ozone precursors (O(3)), and aerosols for climate (expressed in terms of the radiative forcing metric or changes in global surface temperature) and hemispheric-to-continental scale air quality. Reducing the O(3) precursor CH(4) would slow near-term warming by decreasing both CH(4) and tropospheric O(3). Uncertainty remains as to the net climate forcing from anthropogenic nitrogen oxide (NO(x)) emissions, which increase tropospheric O(3) (warming) but also increase aerosols and decrease CH(4) (both cooling). Anthropogenic emissions of carbon monoxide (CO) and non-CH(4) volatile organic compounds (NMVOC) warm by increasing both O(3) and CH(4). Radiative impacts from secondary organic aerosols (SOA) are poorly understood. Black carbon emission controls, by reducing the absorption of sunlight in the atmosphere and on snow and ice, have the potential to slow near-term warming, but uncertainties in coincident emissions of reflective (cooling) aerosols and poorly constrained cloud indirect effects confound robust estimates of net climate impacts. Reducing sulfate and nitrate aerosols would improve air quality and lessen interference with the hydrologic cycle, but lead to warming. A holistic and balanced view is thus needed to assess how air pollution controls influence climate; a first step towards this goal involves estimating net climate impacts from individual emission sectors. Modeling and observational analyses suggest a warming climate degrades air quality (increasing surface O(3) and particulate matter) in many populated regions, including during pollution episodes. Prior Intergovernmental Panel on Climate Change (IPCC) scenarios (SRES) allowed unconstrained growth, whereas the Representative Concentration Pathway (RCP) scenarios assume uniformly an aggressive reduction, of air pollutant emissions. New estimates from the current generation of chemistry-climate models with RCP emissions thus project improved air quality over the next century relative to those using the IPCC SRES scenarios. These two sets of projections likely bracket possible futures. We find that uncertainty in emission-driven changes in air quality is generally greater than uncertainty in climate-driven changes. Confidence in air quality projections is limited by the reliability of anthropogenic emission trajectories and the uncertainties in regional climate responses, feedbacks with the terrestrial biosphere, and oxidation pathways affecting O(3) and SOA.

Ependymoma with "granular cell" features: report of two cases.

We report two cases of ependymoma which showed prominent "granular cell" changes of the cytoplasm. The patients were a 7-year-old boy with a tumor in the cerebellum (case 1) and a 70-year-old man with a tumor in the frontal lobe (case 2). The tumor of case 1 showed a histopathological appearance of ependymoma containing many focal aggregates of large polygonal cells in which the cytoplasm was stuffed with numerous eosinophilic granules. The tumor of case 2 predominantly showed the features of papillary ependymoma, and some tumor cells were swollen and contained similar eosinophilic granules. Intracytoplasmic granules in both tumors were immunoreactive for GFAP and ubiquitin, but not for epithelial membrane antigen, CD68 or mitochondria. Ultrastructurally, they were found as aggregates of membrane-bound, electron-dense, globular structures. Karyotypic analysis of the tumor in case 1 demonstrated 2, 11 and 12 trisomies. Intracytoplasmic eosinophilic granules occasionally occur in astrocytic and oligodendroglial neoplasms, but an appearance of similar granules is very rare in ependymoma. The two cases presented here may represent a new histopathological variant of ependymoma, and the term "granular cell ependymoma" is appropriate for them.

"Bibloc advancement" with a combination of internal and external distracters.

Frontofacial monobloc advancement is one of the most rewarding techniques for correcting aesthetic and functional problems of patients with severe craniofacial synostosis, which can advance the upper and middle third of the face simultaneously. Application of gradual distraction technique has been reported to reduce notorious risks after a frontofacial monobloc advancement. The so-called "bibloc advancement" is a derivative of the frontofacial monobloc advancement. "Facial bloc" is horizontally divided into 2 different components: fronto-orbital component and maxillozygomatic component. From a different angle, it can be described as a combination of fronto-orbital advancement and Le Fort III advancement. Two pairs of distracters (1 internal for the supraorbital area and 1 external for the maxillozygomatic area with a pair of cross-facial pinning) were applied after the so-called bibloc osteotomy. Advancement of the upper and middle third of the face was done individually. This technique can be a good option for treating infants with severe syndromic craniofacial synostosis.

Large-scale serosurveillance of COVID-19 in Japan: Acquisition of neutralizing antibodies for Delta but not for Omicron and requirement of booster vaccination to overcome the Omicron's outbreak.

Continuous appearance of SARS-CoV-2 variants and mass vaccination have been intricately influencing on the COVID-19 situation. To elucidate the current status in Japan, we analyzed totally 2,000 sera in August (n = 1,000) and December (n = 1,000) 2021 collected from individuals who underwent a health check-up. The anti-N seropositive rate were 2.1% and 3.9% in August and December 2021, respectively, demonstrating a Delta variant endemic during that time; it was approximately twofold higher than the rate based on the PCR-based diagnosis. The anti-S seropositive rate was 38.7% in August and it reached 90.8% in December, in concordance with the vaccination rate in Japan. In the December cohort, 78.7% of the sera showed neutralizing activity against the Delta variant, whereas that against the Omicron was much lower at 36.6%. These analyses revealed that effective immunity against the Delta variant was established in December 2021, however, prompt three-dose vaccination is needed to overcome Omicron's outbreak.

[The study of spinal abnormalities associated with cloacal exstrophy].

The treatment of spinal abnormalities with cloacal exstrophy is controversial. Ten cases of this complex treated at Hyogo Prefectural Kobe Children's Hospital between 1991 and 2010 are presented. In our series, all 10 patients had tethered spinal cords. In addition, there were 3 terminal myelocystoceles, 2 meningoceles, 7 lipomas, 5 thickened filums and 3 syrinxes. Eight of 10 patients underwent surgery, and no patient deteriorated. All 3 patients with terminal myelocystocele had lower extremity weakness, but motor functions in two patients improved after surgery. All 4 patients with lipoma and/or thickened filum were asymptomatic. Two of them were conservatively treated, and they remain asymptomatic. Terminal myelocystocele and symptomatic syrinx should be surgically treated.

[Multidisciplinary treatment for severe syndromic craniosynostosis].

We describe the treatment of patients having syndromic craniosynostosis with severe craniofacial abnormality. One patient had Cruzon's syndrome, one had Beare-Stevenson cutis gyrata syndrome, and four had Pfeiffers syndrome. Anterior cranial deformity in all patients was treated using fronto-orbital advancement (FOA) by gradual distraction. Initially, the frontal and supraorbital bones were removed and remodeled. Next, the frontal bones were fixed loosely to the supraorbital bones with absorbable threads. Then, the supraorbital and temporal bones were connected using distraction devices on both sides. The temporal bones were thereafter reinforced with titanium plates. Distraction was started one week postoperation, and the mean amount of elongation was 28.9 mm. Distraction devices were removed one to five months after the operation. One case required FOA by the traditional method ten months after the initial operation. Local infection was observed in three cases, but there were no majors complications. Posterior cranial remodelings were performed in five cases, with one requiring a second operation. We chose the appropriate procedure according to the degree of cranial deformity and operative findings. We performed decompression of the foramen magnum in five cases and laminectomy of the atlas in two cases. Ventriculoperitoneal shunt for hydrocephalus and tracheotomy for airway obstruction were performed in all cases. Cranial remodeling for treating severe craniofacial abnormality requires careful inspection of abnormalities, proper timing, close attention to the procedure and adequate perioperative care. Multidisciplinary therapy is essential for treating severe syndromic craniosynostosis due to systematic osseocartilaginous aplasia.

A case of cerebellar capillary hemangioma with multiple cysts.

Intracranial capillary hemangiomas are very rare, though several spinal capillary hemangiomas have recently been reported. We report here a case of intracranial capillary hemangioma with multiple cysts and review the current literature of similar cases. A 4-month-old girl was referred to our hospital for treatment of hydrocephalus and a cerebellar mass lesion. She presented with hemangiomas distributed widely over the body, as well as disseminated hemangiomas in the pleura, liver, spleen, pancreas, kidneys and vagina. Pathological examination of the specimen from the vagina confirmed the diagnosis of a capillary hemangioma made at another hospital. Radiological examination of the brain revealed a cystic mass lesion in the left cerebellar hemisphere with subsequent obstructive hydrocephalus. The cysts extended upward into the bilateral ventricle. Following neuroendoscopic fenestration of the cysts, resection of the left cerebellar mass was performed. Histological examination of the lesion demonstrated similarly sized capillaries, and the pathological diagnosis was confirmed as capillary hemangioma. There was no recurrence postoperatively. Our patient was treated successfully by surgical resection and neuroendoscopic procedures. Surgical intervention may therefore be indicated in intracranial capillary hemangiomas.

Lateral orbital expansion and gradual fronto-orbital advancement: an option to treat severe syndromic craniosynostosis.

In some patients with severe syndromic craniosynostosis, bony orbits are so small and shallow that the eyeballs dislocate. Dry cornitis and conjunctivitis can be seen often. When conventional fronto-orbital advancement is attempted in these cases, side walls of the orbit cannot go forward, because the width of bony orbit is smaller than the eyeball. To expand bony orbits and cranial volume, supralateral rim of the orbit was expanded laterally at the time of operation and gradually advanced foward postoperatively. With a coronal skin incision approach, frontal bone was taken off. Supralateral orbital rim bone was detached and cut at the centers of the orbits. Lateral expansion, 5 to 10 mm, was made and fixed with polylactate plates. A pair of distraction devices was fixed between the orbital rim and the temporal bone. Frontal bone was let floating on the dura mater and tied loosely with the orbital rim. Advancement of 1 to 1.5 mm/d was carried out, and the devices were taken off after 1-month consolidation period. Five patients with Pfeiffer syndrome, 1 with Crouzon, and 1 with Beare-Stevenson cutis gyrata syndrome were treated with this method. Procedure, outcomes, and complications are discussed.

[Management of chiasmatic-hypothalamic gliomas in children: report of nine pediatric cases].

Radical resection of chiasmatic-hypothalamic glioma (CHG) carries a significant risk of morbidity and the optimum treatment remains undecided. The authors reported 9 children with CHG, who were treated with surgical resection with or without postoperative chemotherapy. Age at the time of diagnosis ranged from 4 months to 7.7 years (mean 3.1 years), and no patient had evidence of neurofibromatosis type 1. Surgical resections of the tumors were performed in all patients because of severe visual impairment or intracranial hypertension caused by large tumors. All of the surgical interventions resulted in partial resections. Pathological examination revealed pilocytic astrocytomas in 7 patients, low grade astrocytoma in 1 and anaplastic astrocytoma in 1. Seven patients with residual tumors received postoperative chemotherapy consisting of cisplatin, cyclophosphamide, etoposide and vincristine. Reduction in tumor size was noticed in 5 patients, although 2 patients had no response and switched to local radiotherapy. Although minor complications of chemotherapy were noticed in 5 patients, severe sequelae such as neuropsychological deficits or endocrinopathies did not occur, and all patients completed chemotherapy programs. Additional treatments are recommended in case of incomplete tumor resections, because our experience demonstrates that the majority of the residual tumors have potential to progress. Our present data suggests that the chemotherapy of the aforementioned regimen is effective in controlling CHGs after partial resections and is relatively well tolerated even in young children who are vulnerable to radiotherapy.

Varying sensitivity of mountainous streamwater base-flow [Formula: see text]concentrations to N deposition in the northern suburbs of Tokyo.

Ecosystems of suburban landscapes (i.e., forest, inland water ecosystem) are threatened by high nitrogen (N) loadings derived from urban air pollutants. Forest ecosystems under high chronic N loadings tend to leach more N via streams. In the northern suburbs of Tokyo, N deposition loading on terrestrial ecosystems has increased over the past 30 years. In this region, we investigated nitrate concentrations in 608 independent small forested catchment water samples from northeastern suburbs of Tokyo. The nitrate concentrations varied from 0.07 to 3.31 mg-N L-1 in this region. We evaluated the effects of N deposition and catchment properties (e.g., meteorological and topographic factors, vegetation and soil types) on nitrate concentrations. In the random forest model, simulated N deposition rates from an atmospheric chemistry transportation model explained most of the variance of nitrate concentration. To evaluate the effects of afforestation management in the catchment, we followed a model-based recursive partitioning method (MOB). MOB succeeded in data-driven identification of subgroups with varying sensitivities to N deposition rate by vegetation composition in the catchment. According to MOB, the catchment with dominant coniferous coverage that mostly consisted of plantation with old tree age tended to have strong sensitivity of nitrate concentrations to N deposition loading.

[Ganglioglioma of the medulla oblongata: case report and review of the literature].

The authors present a pediatric case of ganglioglioma occurring in the medulla oblongata. A 7-year-old boy was referred to our hospital with complaints of ataxia, seizure and sleep apnea. MRI of the brain disclosed a large tumor occupying the medulla oblongata, and the upper portion of the cervical spinal cord was also involved. The patient underwent midline suboccipital craniotomy and laminectomy of C1 to attempt radical resection of the tumor, which resulted only in partial removal of the tumor due to severe bradycardia during the operation. The histological diagnosis was ganglioglioma, WHO grade 2. Although both radiotherapy and chemotherapy were performed following the operation, the tumor remained unchanged. The patient died of respiratory arrest five months after the operation. Gangliogliomas usually occur in the supratentorial region, which permits easy surgical access and good prognosis. Only 3% of gangliogliomas occur in the brain stem, and its management can be challenging because of the difficulty of radical resection and poor response to both radiotherapy and chemotherapy.

Projecting ozone-related mortality in East China.

BACKGROUND: The concentrations of ozone (O3) in China are increasing, especially in East China, but its future trends and potential health impacts remain to be explored. OBJECTIVES: The objective was to assess future trends in O3 concentrations and related premature death in East China between 2005 and 2030. METHODS: First, a global chemical transport model (MIROC-ESM-CHEM) and regional chemical transport modelling system (including the Weather Research and Forecasting model and the Community Multiscale Air Quality model) were combined to estimate daily O3 concentrations in 2005 and 2030 in East China under the "current legislation" (CLE) and "maximum technically feasible reduction" (MFR) scenarios which were applied globally. O3 concentrations were then linked with population projections, mortality projections, and O3-mortality associations to estimate changes in O3-related mortality in East China. RESULTS: The annual mean O3 concentration was projected to increase in East China between 2005 and 2030 under the CLE scenario, while decrease under the MFR scenario. Under the CLE scenario, O3-attributable health burden could increase by at least 40,000 premature deaths in East China, without considering the population growth. Under the MFR scenario, the health burden could decrease by up to 260,000 premature deaths as a result of the reduction in O3 concentration with a static population. However, when the population growth was considered, O3-attributable health burden could increase by up to 46,000 premature deaths in East China under the MFR scenario. CONCLUSIONS: The results suggest that the health burden attributable to O3 may increase in East China in 2030.

The effect of future ambient air pollution on human premature mortality to 2100 using output from the ACCMIP model ensemble.

Ambient air pollution from ground-level ozone and fine particulate matter (PM2.5) is associated with premature mortality. Future concentrations of these air pollutants will be driven by natural and anthropogenic emissions and by climate change. Using anthropogenic and biomass burning emissions projected in the four Representative Concentration Pathway scenarios (RCPs), the ACCMIP ensemble of chemistry-climate models simulated future concentrations of ozone and PM2.5 at selected decades between 2000 and 2100. We use output from the ACCMIP ensemble, together with projections of future population and baseline mortality rates, to quantify the human premature mortality impacts of future ambient air pollution. Future air pollution-related premature mortality in 2030, 2050 and 2100 is estimated for each scenario and for each model using a health impact function based on changes in concentrations of ozone and PM2.5 relative to 2000 and projected future population and baseline mortality rates. Additionally, the global mortality burden of ozone and PM2.5 in 2000 and each future period is estimated relative to 1850 concentrations, using present-day and future population and baseline mortality rates. The change in future ozone concentrations relative to 2000 is associated with excess global premature mortality in some scenarios/periods, particularly in RCP8.5 in 2100 (316 thousand deaths/year), likely driven by the large increase in methane emissions and by the net effect of climate change projected in this scenario, but it leads to considerable avoided premature mortality for the three other RCPs. However, the global mortality burden of ozone markedly increases from 382,000 (121,000 to 728,000) deaths/year in 2000 to between 1.09 and 2.36 million deaths/year in 2100, across RCPs, mostly due to the effect of increases in population and baseline mortality rates. PM2.5 concentrations decrease relative to 2000 in all scenarios, due to projected reductions in emissions, and are associated with avoided premature mortality, particularly in 2100: between -2.39 and -1.31 million deaths/year for the four RCPs. The global mortality burden of PM2.5 is estimated to decrease from 1.70 (1.30 to 2.10) million deaths/year in 2000 to between 0.95 and 1.55 million deaths/year in 2100 for the four RCPs, due to the combined effect of decreases in PM2.5 concentrations and changes in population and baseline mortality rates. Trends in future air pollution-related mortality vary regionally across scenarios, reflecting assumptions for economic growth and air pollution control specific to each RCP and region. Mortality estimates differ among chemistry-climate models due to differences in simulated pollutant concentrations, which is the greatest contributor to overall mortality uncertainty for most cases assessed here, supporting the use of model ensembles to characterize uncertainty. Increases in exposed population and baseline mortality rates of respiratory diseases magnify the impact on premature mortality of changes in future air pollutant concentrations and explain why the future global mortality burden of air pollution can exceed the current burden, even where air pollutant concentrations decrease.