Global proteomic assessment of the classical protein-tyrosine phosphatome and "Redoxome".

Protein-tyrosine phosphatases (PTPs), along with protein-tyrosine kinases, play key roles in cellular signaling. All Class I PTPs contain an essential active site cysteinyl residue, which executes a nucleophilic attack on substrate phosphotyrosyl residues. The high reactivity of the catalytic cysteine also predisposes PTPs to oxidation by reactive oxygen species, such as H(2)O(2). Reversible PTP oxidation is emerging as an important cellular regulatory mechanism and might contribute to diseases such as cancer. We exploited these unique features of PTP enzymology to develop proteomic methods, broadly applicable to cell and tissue samples, that enable the comprehensive identification and quantification of expressed classical PTPs (PTPome) and the oxidized subset of the PTPome (oxPTPome). We find that mouse and human cells and tissues, including cancer cells, display distinctive PTPomes and oxPTPomes, revealing additional levels of complexity in the regulation of protein-tyrosine phosphorylation in normal and malignant cells.

The ubiquitin ligase HERC4 suppresses MafA transcriptional activity triggered by GSK3ß in myeloma by atypical K63-linked polyubiquitination.

MafA and c-Maf are close members of the Maf transcription factor family and indicators of poor prognosis of multiple myeloma (MM). Our previous study finds that the ubiquitin ligase HERC4 induces c-Maf degradation but stabilizes MafA, and the mechanism is elusive. In the present study, we find that HERC4 interacts with MafA and mediates its K63-linked polyubiquitination at K33. Moreover, HERC4 inhibits MafA phosphorylation and its transcriptional activity triggered by glycogen synthase kinase 3ß (GSK3ß). The K33R MafA variant prevents HERC4 from inhibiting MafA phosphorylation and increases MafA transcriptional activity. Further analyses reveal that MafA can also activate the STAT3 signaling, but it is suppressed by HERC4. Lastly, we demonstrate that lithium chloride, a GSK3ß inhibitor, can upregulate HERC4 and synergizes dexamethasone, a typical anti-MM drug, in inhibiting MM cell proliferation and xenograft growth in nude mice. These findings thus highlight a novel regulation of MafA oncogenic activity in MM and provide the rationale by targeting HERC4/GSK3ß/MafA for the treatment of MM.

Left Ventricular Ejection Fraction in Patients With Ovarian Cancer Treated With Avelumab, Pegylated Liposomal Doxorubicin, or Both.

In the phase III JAVELIN Ovarian 200 trial, 566 patients with platinum-resistant/refractory ovarian cancer were randomized 1:1:1 to receive avelumab alone, avelumab plus pegylated liposomal doxorubicin (PLD), or PLD alone. Cardiac monitoring was included for all patients. We report left ventricular ejection fraction (LVEF) data from the trial. Grade ≥3 cardiac adverse events (AEs) occurred in 4 (2.1%), 1 (0.5%), and 0 patients in the avelumab, combination, and PLD arms, respectively. LVEF decreases of ≥10% to below institutional lower limit of normal at any time during treatment were observed in 1 (0.8%), 3 (1.9%), and 2 (1.5%) patients, respectively; 4 had subsequent assessments, and these showed transient decreases. No patient had a cardiovascular AE related to LVEF decrease. This analysis is, to our knowledge, the first analysis of LVEF in patients receiving immune checkpoint inhibitors. CLINICALTRIALS.GOV IDENTIFIER: NCT02580058.

Targeting the Otub1/c-Maf axis for the treatment of multiple myeloma.

The oncogenic transcription factor c-Maf has been proposed as an ideal therapeutic target for multiple myeloma (MM), but how to achieve it is still elusive. In the present study, we found the Otub1/c-Maf axis could be a potential target. Otub1, an OTU family deubiquitinase, was found to interact with c-Maf by mass spectrometry. Otub1 abrogates c-Maf K48-linked polyubiquitination, thus preventing its degradation and enhancing its transcriptional activity. Specifically, this deubiquitinating activity depends on its Lys71 and the N terminus but is independent of UBE2O, a known E2 of c-Maf. Otub1 promotes MM cell survival and MM tumor growth. In contrast, silence of Otub1 leads to c-Maf degradation and c-Maf-expressing MM cell apoptosis. Therefore, the Otub1/c-Maf axis could be a therapeutic target of MM. In order to explore this concept, we performed a c-Maf recognition element-driven luciferase-based screen against US Food and Drug Administration-approved drugs and natural products, from which the generic cardiac glycoside lanatoside C (LanC) is found to prevent c-Maf deubiquitination and induces its degradation by disrupting the interaction of Otub1 and c-Maf. Consequently, LanC inhibits c-Maf transcriptional activity, induces c-Maf-expressing MM cell apoptosis, and suppresses MM growth and prolongs overall survival of model mice, but without apparent toxicity. Therefore, the present study identifies Otub1 as a novel deubiquitinase of c-Maf and establishes that the Otub1/c-Maf axis is a potential therapeutic target for MM.

Training home visitors in mentalization-based practice: A qualitative case study of clinical supervision in mothering from the inside out.

Attachment-based interventions are important for improving parent-child outcomes. These interventions must be scaled and made available to under-resourced communities. An important part of scaling these interventions is delineating and reproducing high-quality training, including clinical training which often requires the completion of a supervised case. However, descriptions and guidelines for clinical training are frequently broad or not available in the literature. A detailed description of clinical training could lead to further research to improve the effectiveness and dissemination of evidence-based interventions. Mothering from the Inside Out (MIO) is an attachment-based parenting intervention effective at reducing substance use and depression, improving caregiving, and enhancing child attachment. It is now being brought from research to community settings. This paper outlines the didactic and clinical training components of MIO. We then present a qualitative case study of one community-based counselor participating in the clinical training of MIO and employ qualitative methods to describe the main themes that arose during the training. We aim to illustrate how the trainer assisted the counselor in implementing the core components of MIO, which included (a) refining the language used in MIO sessions, (b) making space to explore mental states, and (c) addressing trauma. We conclude by presenting the implications of these findings.

Las intervenciones con base en la afectividad son importantes para mejorar los resultados de relación progenitor-niño. Estas intervenciones deben ser adaptadas y estar disponibles para comunidades sin recursos suficientes. Una parte importante de la adaptación de estas intervenciones es delinear y reproducir el entrenamiento de alta calidad, incluyendo entrenamiento clínico que a menudo requiere completar un caso supervisado. Sin embargo, las descripciones y los parámetros de guía para entrenamiento clínico son frecuentemente generales o no están disponibles en el material escrito. Una detallada descripción del entrenamiento clínico pudiera llevar a una posterior investigación para mejorar la eficacia y diseminación de intervenciones con base en la afectividad. Cuidados Maternales de Adentro Hacia Afuera (MIO) es una intervención de crianza con base en la afectividad que es eficaz para reducir el uso de sustancias y la depresión, mejorar la prestación de cuidado y fortalecer la afectividad del niño. Ahora se le lleva de la investigación a los escenarios comunitarios. Este artículo subraya los componentes de didáctica y entrenamiento clínico de MIO. Presentamos entonces un caso de estudio cualitativo de un consejero con base en la comunidad que participó en el entrenamiento clínico de MIO y empleamos métodos cualitativos para describir los temas principales que surgieron durante el entrenamiento. Nos propusimos ilustrar cómo el entrenador ayudó al consejero a implementar los componentes centrales de MIO, los cuales incluyen (a) refinar el lenguaje usado en la terapia, (b) abrir un espacio para explorar estados mentales, y (c) ocuparse del trauma. Concluimos con la presentación de las implicaciones que conllevan estos resultados.

Les interventions basées sur l'attachement sont importantes quand il s'agit d'améliorer les résultats parent-enfant. Ces interventions doivent être mises à l'échelle et doivent être disponibles pour toutes les communautés ayant peu de moyens. Un côté important de la mise à l'échelle de ces interventions consiste à délinéer et à reproduire une formation de haute qualité, y compris une formation clinique qui souvent exige la réalisation d'un cas supervisé. Cependant les descriptions et les lignes directrices de la formation clinique sont fréquemment larges ou ne sont pas disponibles dans des publications. Une description détaillée de formation Clinique pourrait conduire à des recherches approfondies sur la manière d'améliorer l'efficacité et la dissémination d'interventions fondées sur des données probantes. Le maternage de l'intérieur (abrégé ici MIO pour reprendre l'anglais Mothering from the Inside Out) est une intervention de parentage basée sur l'attachement qui est efficace pour ce qui concerne la réduction de toxicomanie et de dépression, l'amélioration des soins ainsi que de l'attachement de l'enfant. On le fait en ce moment passer des recherches aux contextes communautaires. Cet article décrit les composantes de formation didactique et clinique du MIO. Nous présentons ensuite une étude de cas qualitative d'un thérapeute communautaire participant à une formation clinique du MOI et employons des méthodes qualitatives pour décrire les thèmes principaux qui sont apparus durant la formation. Nous nous donnons pour but d'illustrer la manière dont le formateur a aidé le thérapeute à mettre en place les composantes essentielles du MIO, y compris (a) l'affinage du langage utilisé en thérapie, (b) la nécessité de faire de la place afin d'explorer les états mentaux, et (c) la nécessité d'aborder le trauma. Nous concluons en présentant les implications de ces résultats.

Oncohistone interactome profiling uncovers contrasting oncogenic mechanisms and identifies potential therapeutic targets in high grade glioma.

Histone H3 mutations at amino acids 27 (H3K27M) and 34 (H3G34R) are recurrent drivers of pediatric-type high-grade glioma (pHGG). H3K27M mutations lead to global disruption of H3K27me3 through dominant negative PRC2 inhibition, while H3G34R mutations lead to local losses of H3K36me3 through inhibition of SETD2. However, their broader oncogenic mechanisms remain unclear. We characterized the H3.1K27M, H3.3K27M and H3.3G34R interactomes, finding that H3K27M is associated with epigenetic and transcription factor changes; in contrast H3G34R removes a break on cryptic transcription, limits DNA methyltransferase access, and alters mitochondrial metabolism. All 3 mutants had altered interactions with DNA repair proteins and H3K9 methyltransferases. H3K9me3 was reduced in H3K27M-containing nucleosomes, and cis-H3K9 methylation was required for H3K27M to exert its effect on global H3K27me3. H3K9 methyltransferase inhibition was lethal to H3.1K27M, H3.3K27M and H3.3G34R pHGG cells, underscoring the importance of H3K9 methylation for oncohistone-mutant gliomas and suggesting it as an attractive therapeutic target.

A drug discovery platform to identify compounds that inhibit EGFR triple mutants.

Receptor tyrosine kinases (RTKs) are transmembrane receptors of great clinical interest due to their role in disease. Historically, therapeutics targeting RTKs have been identified using in vitro kinase assays. Due to frequent development of drug resistance, however, there is a need to identify more diverse compounds that inhibit mutated but not wild-type RTKs. Here, we describe MaMTH-DS (mammalian membrane two-hybrid drug screening), a live-cell platform for high-throughput identification of small molecules targeting functional protein-protein interactions of RTKs. We applied MaMTH-DS to an oncogenic epidermal growth factor receptor (EGFR) mutant resistant to the latest generation of clinically approved tyrosine kinase inhibitors (TKIs). We identified four mutant-specific compounds, including two that would not have been detected by conventional in vitro kinase assays. One of these targets mutant EGFR via a new mechanism of action, distinct from classical TKI inhibition. Our results demonstrate how MaMTH-DS is a powerful complement to traditional drug screening approaches.

The deubiquitinase USP7 stabilizes Maf proteins to promote myeloma cell survival.

The Maf proteins, including c-Maf, MafA, and MafB, are critical transcription factors in myelomagenesis. Previous studies demonstrated that Maf proteins are processed by the ubiquitin-proteasome pathway, but the mechanisms remain elusive. This study applied MS to identify MafB ubiquitination-associated proteins and found that the ubiquitin-specific protease USP7 was present in the MafB interactome. Moreover, USP7 also interacted with c-Maf and MafA and blocked their polyubiquitination and degradation. Consistently, knockdown of USP7 resulted in Maf protein degradation along with increased polyubiquitination levels. The action of USP7 thus promoted Maf transcriptional activity as evidenced by luciferase assays and by the up-regulation of the expression of Maf-modulated genes. Furthermore, USP7 was up-regulated in myeloma cells, and it was negatively associated with the survival of myeloma patients. USP7 promoted myeloma cell survival, and when it was inhibited by its specific inhibitor P5091, myeloma cell lines underwent apoptosis. These results therefore demonstrated that USP7 is a deubiquitinase of Maf proteins and promotes MM cell survival in association with Maf stability. Given the significance of USP7 and Maf proteins in myeloma genesis, targeting the USP7/Maf axle is a potential strategy to the precision therapy of MM.

Extracellular phosphorylation drives the formation of neuronal circuitry.

Until recently, the existence of extracellular kinase activity was questioned. Many proteins of the central nervous system are targeted, but it remains unknown whether, or how, extracellular phosphorylation influences brain development. Here we show that the tyrosine kinase vertebrate lonesome kinase (VLK), which is secreted by projecting retinal ganglion cells, phosphorylates the extracellular protein repulsive guidance molecule b (RGMb) in a dorsal-ventral descending gradient. Silencing of VLK or RGMb causes aberrant axonal branching and severe axon misguidance in the chick optic tectum. Mice harboring RGMb with a point mutation in the phosphorylation site also display aberrant axonal pathfinding. Mechanistic analyses show that VLK-mediated RGMb phosphorylation modulates Wnt3a activity by regulating LRP5 protein gradients. Thus, the secretion of VLK by projecting neurons provides crucial signals for the accurate formation of nervous system circuitry. The dramatic effect of VLK on RGMb and Wnt3a signaling implies that extracellular phosphorylation likely has broad and profound effects on brain development, function and disease.

Refined RIP-seq protocol for epitranscriptome analysis with low input materials.

N6-Methyladenosine (m6A) accounts for approximately 0.2% to 0.6% of all adenosine in mammalian mRNA, representing the most abundant internal mRNA modifications. m6A RNA immunoprecipitation followed by high-throughput sequencing (MeRIP-seq) is a powerful technique to map the m6A location transcriptome-wide. However, this method typically requires 300 µg of total RNA, which limits its application to patient tumors. In this study, we present a refined m6A MeRIP-seq protocol and analysis pipeline that can be applied to profile low-input RNA samples from patient tumors. We optimized the key parameters of m6A MeRIP-seq, including the starting amount of RNA, RNA fragmentation, antibody selection, MeRIP washing/elution conditions, methods for RNA library construction, and the bioinformatics analysis pipeline. With the optimized immunoprecipitation (IP) conditions and a postamplification rRNA depletion strategy, we were able to profile the m6A epitranscriptome using 500 ng of total RNA. We identified approximately 12,000 m6A peaks with a high signal-to-noise (S/N) ratio from 2 lung adenocarcinoma (ADC) patient tumors. Through integrative analysis of the transcriptome, m6A epitranscriptome, and proteome data in the same patient tumors, we identified dynamics at the m6A level that account for the discordance between mRNA and protein levels in these tumors. The refined m6A MeRIP-seq method is suitable for m6A epitranscriptome profiling in a limited amount of patient tumors, setting the ground for unraveling the dynamics of the m6A epitranscriptome and the underlying mechanisms in clinical settings.

Real-world outcomes in patients with metastatic renal cell carcinoma according to risk factors: the STAR-TOR registry.

Aim: Examine outcomes in sunitinib-treated patients by International Metastatic RCC Database Consortium (IMDC) or Memorial Sloan-Kettering Cancer Center (MSKCC) risk factors. Patients & methods: Patients enrolled in STAR-TOR registry (n = 327). End points included overall survival, progression-free survival and objective response rate. Results: Overall survival was similar for IMDC 0 versus 1 (p = 0.238) or 2 versus ≥3 (p = 0.156), but different for MSKCC (0 vs 1, p = 0.037; 2 vs ≥3, p = 0.001). Progression-free survival was similar for IMDC 2 versus 3 (p = 0.306), but different for MSKCC (p = 0.009). Objective response rate was different for IMDC 1 (41.9%) and 2 (29.5%) and similar for MSKCC 1 (34.4%) and 2 (31.0%). Conclusion: Outcome data varied according to IMDC or MSKCC. MSKCC model accurately stratify patients into risk groups. Clinical trial registration: NCT00700258 (ClinicalTrials.gov).

Prediction of LC-MS/MS Properties of Peptides from Sequence by Deep Learning.

Deep learning models for prediction of three key LC-MS/MS properties from peptide sequences were developed. The LC-MS/MS properties or behaviors are indexed retention times (iRT), MS1 or survey scan charge state distributions, and sequence ion intensities of HCD spectra. A common core deep supervised learning architecture, bidirectional long-short term memory (LSTM) recurrent neural networks was used to construct the three prediction models. Two featurization schemes were proposed and demonstrated to allow for efficient encoding of modifications. The iRT and charge state distribution models were trained with on order of 105 data points each. An HCD sequence ion prediction model was trained with 2 × 106 experimental spectra. The iRT prediction model and HCD sequence ion prediction model provide improved accuracies over the start-of-the-art models available in literature. The MS1 charge state distribution prediction model offers excellent performance. The prediction models can be used to enhance peptide identification and quantification in data-dependent acquisition and data-independent acquisition (DIA) experiments as well as to assist MRM (multiple reaction monitoring) and PRM (parallel reaction monitoring) experiment design.

Organizational characteristics associated with high performance on quality measures in pediatric primary care: A positive deviance study.

BACKGROUND: Pediatric health care quality in the United States varies, but the reasons for variation are not fully understood. Differences in pediatric practices' organizational characteristics, such as organizational structures, strategies employed to improve quality, and other contextual factors, may contribute to the variation observed. PURPOSE: To assess the relationship between organizational characteristics and performance on clinical quality (CQ) and patient experience (PE) measures in primary care pediatric practices in Massachusetts. METHODOLOGY: A 60-item questionnaire that assessed the presence of selected organizational characteristics was sent to 172 pediatric practice managers in Massachusetts between December 2017 and February 2018. The associations between select organizational characteristics and publicly available CQ and PE scores were analyzed using analysis of variance; open-ended survey questions were analyzed using qualitative content analysis. RESULTS: Eighty-six practices (50.0%) responded; 80 (46.5%) were included in the primary analysis. Having a quality champion ( p = .03), offering co-located specialty services (e.g., behavioral health; p = .04), being a privately owned practice ( p = .04), believing that patients and families feel respected ( p = .03), and having a lower percentage of patients (10%-25%) covered by public health insurance ( p = .04) were associated with higher CQ scores. Higher PE scores were associated with private practice ownership ( p = .0006). Qualitative analysis suggested organizational culture and external factors, such as health care finance, may affect quality. CONCLUSIONS: Both modifiable organizational practices and factors external to a practice may affect quality of care. Addressing differences in practice performance may not be reducible to implementation of changes in single organizational characteristics. PRACTICE IMPLICATIONS: Pediatric practices seeking to improve quality of care may wish to adopt the strategies that were associated with higher performance on quality measures, but additional studies are needed to better understand the mechanisms behind these associations and how they relate to each other.

Discovery of a Low Thermal Conductivity Oxide Guided by Probe Structure Prediction and Machine Learning.

We report the aperiodic titanate Ba10 Y6 Ti4 O27 with a room-temperature thermal conductivity that equals the lowest reported for an oxide. The structure is characterised by discontinuous occupancy modulation of each of the sites and can be considered as a quasicrystal. The resulting localisation of lattice vibrations suppresses phonon transport of heat. This new lead material for low-thermal-conductivity oxides is metastable and located within a quaternary phase field that has been previously explored. Its isolation thus requires a precisely defined synthetic protocol. The necessary narrowing of the search space for experimental investigation was achieved by evaluation of titanate crystal chemistry, prediction of unexplored structural motifs that would favour synthetically accessible new compositions, and assessment of their properties with machine-learning models.

Data Dependent-Independent Acquisition (DDIA) Proteomics.

Data dependent acquisition (DDA) and data independent acquisition (DIA) are traditionally separate experimental paradigms in bottom-up proteomics. In this work, we developed a strategy combining the two experimental methods into a single LC-MS/MS run. We call the novel strategy data dependent-independent acquisition proteomics, or DDIA for short. Peptides identified from DDA scans by a conventional and robust DDA identification workflow provide useful information for interrogation of DIA scans. Deep learning based LC-MS/MS property prediction tools, developed previously, can be used repeatedly to produce spectral libraries facilitating DIA scan extraction. A complete DDIA data processing pipeline, including the modules for iRT vs RT calibration curve generation, DIA extraction classifier training, and false discovery rate control, has been developed. Compared to another spectral library-free method, DIA-Umpire, the DDIA method produced a similar number of peptide identifications, but nearly twice as many protein group identifications. The primary advantage of the DDIA method is that it requires minimal information for processing its data.

Repeat-Preserving Decoy Database for False Discovery Rate Estimation in Peptide Identification.

The sequence database searching method is widely used in proteomics for peptide identification. To control the false discovery rate (FDR) of the searching results, the target-decoy method generates and searches a decoy database together with the target database. A known problem is that the target protein sequence database may contain numerous repeated peptides. The structures of these repeats are not preserved by most existing decoy generation algorithms. Previous studies suggest that such discrepancy between the target and decoy databases may lead to an inaccurate FDR estimation. Based on the de Bruijn graph model, we propose a new repeat-preserving algorithm to generate decoy databases. We prove that this algorithm preserves the structures of the repeats in the target database to a great extent. The de Bruijn method has been compared with a few other commonly used methods and demonstrated superior FDR estimation accuracy and an improved number of peptide identification.

Eight-Year Estimates of Methane Emissions from Oil and Gas Operations in Western Canada Are Nearly Twice Those Reported in Inventories.

The provinces of Alberta and Saskatchewan account for 70% of Canada's methane emissions from the oil and gas sector. In 2018, the Government of Canada introduced methane regulations to reduce emissions from the sector by 40-45% from the 2012 levels by 2025. Complementary to inventory accounting methods, the effectiveness of regulatory practices to reduce emissions can be assessed using atmospheric measurements and inverse models. Total anthropogenic (oil and gas, agriculture, and waste) emission rates of methane from 2010 to 2017 in Alberta and Saskatchewan were derived using hourly atmospheric methane measurements over a six-month winter period from October to March. Scaling up the winter estimate to annual indicated an anthropogenic emission rate of 3.7 ± 0.7 MtCH4/year, about 60% greater than that reported in Canada's National Inventory Report (2.3 MtCH4). This discrepancy is tied primarily to the oil and gas sector emissions as the reported emissions from livestock operations (0.6 MtCH4) are well substantiated in both top-down and bottom-up estimates and waste management (0.1 MtCH4) emissions are small. The resulting estimate of 3.0 MtCH4 from the oil and gas sector is nearly twice that reported in Canada's National Inventory (1.6 MtCH4).

Top-Down Determination of Black Carbon Emissions from Oil Sand Facilities in Alberta, Canada Using Aircraft Measurements.

Black carbon (BC) emissions from the Canadian oil sand (OS) surface mining facilities in Alberta were investigated using aircraft measurements. BC emission rates were derived with a top-down mass balance approach and were found to be linearly related to the volume of oil sand ore mined at each facility. Two emission factors were determined from the measurements; production-based BC emission factors were in the range of 0.6-1.7 g/tonne mined OS ore, whereas fuel-based BC emission factors were between 95 and 190 mg/kg-fuel, depending upon the facility. The annual BC emission, at 707 ± 117 tonnes/year for the facilities, was determined using the production-based emission factors and annual production data. Although this annual emission is in reasonable agreement with the BC annual emissions reported in the latest version of the Canadian national BC inventory (within 16%), the relative split between off-road diesel and stack sources is significantly different between the measurements and the inventory. This measurement evidence highlights the fact that the stack sources of BC may be overestimated and the off-road diesel sources may be underestimated in the inventory and points to the need for improved BC emission data from diesel sources within facilities.

Effect of comorbidities/comedications on sunitinib outcomes for metastatic renal cell carcinoma: the STAR-TOR registry.

Aim: Examine the effects of baseline hypertension (HTN) and statin or proton pump inhibitor (PPI) use on sunitinib treatment outcomes in STAR-TOR, a real-world registry. Materials & methods: Presence or absence of HTN and use or nonuse of statins or PPIs were determined at registry entry. End points included overall survival (OS) and progression-free survival (PFS). Results: Data were from 557 patients. Presence or absence of HTN did not affect OS or PFS. PFS (median [95% CI]) was longer in statin users (9.4 [6.5-13.6] months) versus nonusers (6.9 [5.7-8.2] months) (p = 0.0442). OS was shorter in PPI users (20.2 [14.9-28.3] months) versus nonusers (25.7 [22.7-33.0] months) (p = 0.0212). Conclusion: Comorbidities and comedications may affect real-world sunitinib treatment outcomes. Clinical Trial Registration: NCT00700258 (ClinicalTrials.gov).

Differences between measured and reported volatile organic compound emissions from oil sands facilities in Alberta, Canada.

Large-scale oil production from oil sands deposits in Alberta, Canada has raised concerns about environmental impacts, such as the magnitude of air pollution emissions. This paper reports compound emission rates (E) for 69-89 nonbiogenic volatile organic compounds (VOCs) for each of four surface mining facilities, determined with a top-down approach using aircraft measurements in the summer of 2013. The aggregate emission rate (aE) of the nonbiogenic VOCs ranged from 50 ± 14 to 70 ± 22 t/d depending on the facility. In comparison, equivalent VOC emission rates reported to the Canadian National Pollutant Release Inventory (NPRI) using accepted estimation methods were lower than the aE values by factors of 2.0 ± 0.6, 3.1 ± 1.1, 4.5 ± 1.5, and 4.1 ± 1.6 for the four facilities, indicating underestimation in the reported VOC emissions. For 11 of the combined 93 VOC species reported by all four facilities, the reported emission rate and E were similar; but for the other 82 species, the reported emission rate was lower than E The median ratio of E to that reported for all species by a facility ranged from 4.5 to 375 depending on the facility. Moreover, between 9 and 53 VOCs, for which there are existing reporting requirements to the NPRI, were not included in the facility emission reports. The comparisons between the emission reports and measurement-based emission rates indicate that improvements to VOC emission estimation methods would enhance the accuracy and completeness of emission estimates and their applicability to environmental impact assessments of oil sands developments.