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The Vietnamese National REDD + Action Plan (NRAP) seeks to reduce emissions from forest clearing and land use, especially from the main drivers of coffee and rubber commodity expansion. Achieving the NRAP goals, however, means negotiating a complex and fragmented forest policy arena, with conflicting sector goals, disconnects between global and local ambition and action, and imbalanced power dynamics between actors. We map the fragmentation of this policy arena and explore the extent to which the NRAP is able to integrate policy responses to drivers to achieve emissions reductions. We examine what the NRAP sought to integrate, what was not taken into account, what is integrated at which scale, and which actors are part of integration (or not) across the policy process components. We conclude that if policy integration does not affect a ?whole of government? shift in priorities or change in mandate among driver sectors, fragmented policy arenas will persist and forest based climate mitigation objectives will not be achieved.

BACKGROUND: Air pollution exposure has been associated with increased risk of COVID-19 incidence and mortality by ecological analyses. Few studies have investigated the specific effect of traffic-related air pollution on COVID-19 severity. OBJECTIVE: To investigate the associations of near-roadway air pollution (NRAP) exposure with COVID-19 severity and mortality using individual-level exposure and outcome data. METHODS: The retrospective cohort includes 75,010 individuals (mean age 42.5 years, 54% female, 66% Hispanic) diagnosed with COVID-19 at Kaiser Permanente Southern California between 3/1/2020-8/31/2020. NRAP exposures from both freeways and non-freeways during 1-year prior to the COVID-19 diagnosis date were estimated based on residential address history using the CALINE4 line source dispersion model. Primary outcomes include COVID-19 severity defined as COVID-19-related hospitalizations, intensive respiratory support (IRS), intensive care unit (ICU) admissions within 30 days, and mortality within 60 days after COVID-19 diagnosis. Covariates including socio-characteristics and comorbidities were adjusted for in the analysis. RESULT: One standard deviation (SD) increase in 1-year-averaged non-freeway NRAP (0.5 ppb NOx) was associated with increased odds of COVID-19-related IRS and ICU admission [OR (95% CI): 1.07 (1.01, 1.13) and 1.11 (1.04, 1.19) respectively] and increased risk of mortality (HR = 1.10, 95% CI = 1.03, 1.18). The associations of non-freeway NRAP with COVID-19 outcomes were largely independent of the effect of regional fine particulate matter and nitrogen dioxide exposures. These associations were generally consistent across age, sex, and race/ethnicity subgroups. The associations of freeway and total NRAP with COVID-19 severity and mortality were not statistically significant. CONCLUSIONS: Data from this multiethnic cohort suggested that NRAP, particularly non-freeway exposure in Southern California, may be associated with increased risk of COVID-19 severity and mortality among COVID-19 infected patients. Future studies are needed to assess the impact of emerging COVID-19 variants and chemical components from freeway and non-freeway NRAP.

Importance Previous studies have reported associations between in utero exposure to regional air pollution and autism spectrum disorders (ASD). In utero exposure to components of near-roadway air pollution (NRAP) has been linked to adverse neurodevelopment in animal models, but few studies have investigated NRAP association with ASD risk. Objective To identify ASD risk associated with in utero exposure to NRAP in a large, representative birth cohort. Design, Setting, and Participants This retrospective pregnancy cohort study included 314,391 mother–child pairs of singletons born between 2001 and 2014 at Kaiser Permanente Southern California (KPSC) hospitals. Maternal and child data were extracted from KPSC electronic medical records. Children were followed until: clinical diagnosis of ASD, non-KPSC membership, death, or December 31, 2019, whichever came first. Exposure to the complex NRAP mixture during pregnancy was assessed using line-source dispersion models to estimate fresh vehicle emissions from freeway and non-freeway sources at maternal addresses during pregnancy. Vehicular traffic load exposure was characterized using advanced telematic models combining traditional traffic counts and travel-demand models with cell phone and vehicle GPS data. Cox proportional-hazard models estimated hazard ratios (HR) of ASD associated with near-roadway traffic load and dispersion-modeled NRAP during pregnancy, adjusted for covariates. Non-freeway NRAP was analyzed using quintile distribution due to nonlinear associations with ASD. Exposures Average NRAP and traffic load exposure during pregnancy at maternal residential addresses. Main Outcomes Clinical diagnosis of ASD. Results A total of 6,291 children (5,114 boys, 1,177 girls) were diagnosed with ASD. The risk of ASD was associated with pregnancy-average exposure to total NRAP [HR(95% CI): 1.03(1.00,1.05) per 5 ppb increase in dispersion-modeled NOx] and to non-freeway NRAP [HR(95% CI) comparing the highest to the lowest quintile: 1.19(1.11, 1.27)]. Total NRAP had a stronger association in boys than in girls, but the association with non-freeway NRAP did not differ by sex. The association of freeway NRAP with ASD risk was not statistically significant. Non-freeway traffic load exposure demonstrated associations with ASD consistent with those of NRAP and ASD. Conclusions In utero exposure to near-roadway air pollution, particularly from non-freeway sources, may increase ASD risk in children.

Native cattle breeds represent an important cultural heritage. They are a reservoir of genetic variation useful for properly responding to agriculture needs in the light of ongoing climate changes. Evolutionary processes that occur in response to extreme environmental conditions could also be better understood using adapted local populations. Herein, different evolutionary histories of the world northernmost native cattle breeds from Russia were investigated. They highlighted Kholmogory as a typical taurine cattle, whereas Yakut cattle separated from European taurines approximately 5,000 years ago and contain numerous ancestral and some novel genetic variants allowing their adaptation to harsh conditions of living above the Polar Circle. Scans for selection signatures pointed to several common gene pathways related to adaptation to harsh climates in both breeds. But genes affected by selection from these pathways were mostly different. A Yakut cattle breed-specific missense mutation in a highly conserved NRAP gene represents a unique example of a young amino acid residue convergent change shared with at least 16 species of hibernating/cold-adapted mammals from six distinct phylogenetic orders. This suggests a convergent evolution event along the mammalian phylogenetic tree and fast fixation in a single isolated cattle population exposed to a harsh climate.

This paper summarizes the risk assessment and management workflow developed and applied to the Southwest Regional Partnership on Carbon Sequestration (SWP) Phase III Demonstration Project. The risk assessment and management workflow consists of six primary tasks, including management planning, identification, qualitative analysis, quantitative analysis, response planning, and monitoring. Within the workflow, the SWP assembled and iteratively updated a risk registry that identifies risks for all major activities of the project. Risk elements were ranked with respect to the potential impact to the project and the likelihood of occurrence. Both qualitative and quantitative risk analyses were performed. To graphically depict the interactions among risk elements and help building risk scenarios, process influence diagrams were used to represent the interactions. The SWP employed quantitative methods of risk analysis including Response Surface Method (RSM), Polynomial Chaos Expansion (PCE), and the National Risk Assessment Partnership (NRAP) toolset. The SWP also developed risk response planning and performed risk control and monitoring to prevent the risks from affecting the project and ensure the effectiveness of risk management. As part of risk control and monitoring, existing and new risks have been tracked and the response plan was subsequently evaluated. Findings and lessons learned from the SWP’s risk assessment and management efforts will provide valuable information for other commercial geological CO2 storage projects.

Background Familial dilated cardiomyopathy (DCM) is typically a monogenic disorder with dominant inheritance. Although over 40 genes have been linked to DCM, more than half of the patients undergoing comprehensive genetic testing are left without molecular diagnosis. Recently, biallelic protein-truncating variants (PTVs) in the nebulin-related anchoring protein gene (NRAP) were identified in a few patients with sporadic DCM. Methods and results We determined the frequency of rare NRAP variants in a cohort of DCM patients and control patients to further evaluate role of this gene in cardiomyopathies. A retrospective analysis of our internal variant database consisting of 31,639 individuals who underwent genetic testing (either panel or direct exome sequencing) was performed. The DCM group included 577 patients with either a confirmed or suspected DCM diagnosis. A control cohort of 31,062 individuals, including 25,912 individuals with non-cardiac (control group) and 5,150 with non-DCM cardiac indications (Non-DCM cardiac group). Biallelic (n = 6) or two (n = 5) NRAP variants (two PTVs or PTV+missense) were identified in 11 unrelated probands with DCM (1.9%) but none of the controls. None of the 11 probands had an alternative molecular diagnosis. Family member testing supports co-segregation. Biallelic or potentially biallelic NRAP variants were enriched in DCM vs. controls (OR 1052, pNRAP PTVs in the gnomAD reference population, and predicting full penetrance, biallelic NRAP variants could explain 0.25%-2.46% of all DCM cases. Conclusion Loss-of-function in NRAP is a cause for autosomal recessive dilated cardiomyopathy, supporting its inclusion in comprehensive genetic testing.

Geologic CO2 sequestration (GCS) has received high-level attention from the global scientific community as a response to climate change due to higher concentrations of CO2 in the atmosphere. However, GCS in saline aquifers poses certain risks including CO2/brine leakage through wells or non-sealing faults into groundwater or to the earth’s surface. Understanding crucial reservoir parameters and other geologic features affecting the likelihood of these leakage occurrences will aid the decision-making process regarding GCS operations. In this study, we develop a science-based methodology for quantifying risk profiles at geologic CO2 sequestration sites as part of US DOE’s National Risk Assessment Partnership (NRAP). We apply NRAP tools to a field scale project in a fractured saline aquifer located at Kevin Dome, Montana, which is part of DOE’s Big Sky Carbon Sequestration Partnership project. Risks associated with GCS injection and monitoring are difficult to quantify due to a dearth of data and uncertainties. One solution is running a large number of numerical simulations of the primary CO2 injection reservoir, shallow reservoirs/aquifers, faults, and wells to address leakage risks and uncertainties. However, a full-physics simulation is not computationally feasible because the model is too large and requires fine spatial and temporal discretization to accurately reproduce complex multiphase flow processes. We employ the NRAP Integrated Assessment Model (NRAP-IAM), a hybrid system model developed by the US-DOE for use in performance and quantitative risk assessment of CO2 sequestration. The IAM model requires reduced order models (ROMs) developed from numerical reservoir simulations of a primary CO2 injection reservoir. The ROMs are linked with discrete components of the NRAP-IAM including shallow reservoirs/aquifers and the atmosphere through potential leakage pathways. A powerful stochastic framework allows NRAP-IAM to be used to explore complex interactions among a large number of uncertain variables and to help evaluate the likely performance of potential sequestration sites. Using the NRAP-IAM, we find that the potential amount of CO2 leakage is most sensitive to values of permeability, end-point CO2 relative permeability, hysteresis of CO2 relative permeability, capillary pressure, and permeability of confining rocks. In addition to demonstrating the application of the NRAP risk assessment tools, this work shows that GCS in the Kevin Dome has a higher probability of encountering injectivity limitations during injection of CO2 into the Middle Duperow formation than previous studies have calculated. Finally, we estimate very low risk of CO2 leakage to the atmosphere unless the quality of the legacy well completions is extremely poor.

Background: Dilated cardiomyopathy (DCM) is a progressive, lethal disorder that has heterogeneous genetic background. It has been linked to mutations in Nebulin-related-anchoring protein (NRAP) gene. NRAP expressed mainly in striated and cardiac muscles, and it plays substantial role in the sarcomeric contraction cycle and myofibrillogenesis. Case Presentation: A 17-month-old baby girl presented at the age of 13 months with symptoms of heart failure. She was diagnosed as a case of dilated cardiomyopathy. Using whole exome sequencing, diagnosis is confirmed due to homozygous NRAP variant c.400-407 del p.(Cys134 Serfs*12), which create premature stop codon. Conclusion: This case report supports preceding reports that biallelic deletion mutations in NRAP gene cause an autosomal recessive DCM with low penetrance genetic risk factor. However, the age of presentation can vary from early infancy up to adulthood.

Managing risks at geologic CO 2 storage sites requires making decisions based on the quantitative predictions of long-term performance that not only take into account various subsurface hydrologic, geochemical processes and interactions but also the related uncertainties. The US DOE (United States Department of Energy) funded National Risk Assessment Partnership (NRAP) has developed a quantitative approach and a model to predict the long-term behavior of GCS sites. The approach uses an integrated assessment model (NRAP-IAM-CS) that couples reduced order models (ROMs) for various GCS components (such as storage reservoir, wells, seals, and groundwater aquifer) in a stochastic modeling framework that allows for rapid simulations of entire system behavior over thousands of years while probing uncertainties. We demonstrate application of NRAP-IAM-CS using two examples that focus on CO 2 leakage and resulting impacts. The examples are used to demonstrate how different uncertain parameters affect overall performance objectives.

Hypertrophic cardiomyopathy (HCM) is a heterogenous heart muscle disease predominantly caused by sarcomeric protein encoding genes. However, the cause for a significant number of elderly patients remains unclear. Here, we performed whole-exome sequencing in a South Indian family with an elderly HCM proband. We identified a heterozygous missense variant in the Nebulin-Related-Anchoring Protein encoding geneNRAP(NM_001261463, c.1259A>G, p.Y420C) in the proband. NRAP is a multi-domain scaffolding protein involved in cardiac muscle thin filament assembly, myofibril and actin cytoskeleton organization. The respective NRAP (p.Y420C) is predicted to be pathological byin-silicoanalysis and might be potentially influencing its functions. Targeted re-sequencing in an independent cohort resulted in identification of the same amino acid change in an unrelated eighty-six years old patient. The protein-protein interactions (PPI) network analysis revealed NRAP is strongly associated with other known elderly and late-onset HCM genes/proteins. In line with these data, both the study patients are late-onset in nature. Our study for the first time reveals the association ofNRAPin the elderly and late-onset HCM patients and further expands the genotypic-phenotypic spectrum of HCM.

Nemaline myopathy (NM) is the most common form of congenital myopathy that results in hypotonia and muscle weakness. This disease is clinically and genetically heterogeneous, but three recently discovered genes in NM encode for members of the Kelch family of proteins. Kelch proteins act as substrate-specific adaptors for Cullin 3 (CUL3) E3 ubiquitin ligase to regulate protein turnover through the ubiquitin-proteasome machinery. Defects in thin filament formation and/or stability are key molecular processes that underlie the disease pathology in NM; however, the role of Kelch proteins in these processes in normal and diseases conditions remains elusive. Here, we describe a role of NM causing Kelch protein, KLHL41, in premyofibil-myofibil transition during skeletal muscle development through a regulation of the thin filament chaperone, nebulin-related anchoring protein (NRAP). KLHL41 binds to the thin filament chaperone NRAP and promotes ubiquitination and subsequent degradation of NRAP, a process that is critical for the formation of mature myofibrils. KLHL41 deficiency results in abnormal accumulation of NRAP in muscle cells. NRAP overexpression in transgenic zebrafish resulted in a severe myopathic phenotype and absence of mature myofibrils demonstrating a role in disease pathology. Reducing Nrap levels in KLHL41 deficient zebrafish rescues the structural and function defects associated with disease pathology. We conclude that defects in KLHL41-mediated ubiquitination of sarcomeric proteins contribute to structural and functional deficits in skeletal muscle. These findings further our understanding of how the sarcomere assembly is regulated by disease-causing factors in vivo, which will be imperative for developing mechanism-based specific therapeutic interventions.

Background Evidence suggests that childhood near-roadway air pollution (NRAP) exposures contribute to increased body mass index (BMI); however, effects of NRAP exposure during the vulnerable periods including in utero and first year of life have yet to be established. In this study, we examined whether exposure to elevated concentrations of NRAP during in utero and/or first year of life increase childhood BMI growth. Methods Participants in the Children’s Health Study enrolled from 2002 to 2003 with annual visits over a four-year period and who changed residences before study entry were included (n = 2318). Annual height and weight were measured and lifetime residential NRAP exposures including in utero and first year of life periods were estimated by nitrogen oxides (NOx) using the California line-source dispersion model. Linear mixed effects models assessed in utero or first year near-road freeway and non-freeway NOx exposures and BMI growth after adjusting for age, sex, race/ethnicity, parental education, Spanish questionnaire, and later childhood near-road NOx exposure. Results A two-standard deviation difference in first year of life near-road freeway NOx exposure was associated with a 0.1 kg/m2 (95% confidence interval (CI): 0.03, 0.2) faster increase in BMI growth per year and a 0.5 kg/m2 (95% CI: 0.02, 0.9) higher attained BMI at age 10 years. Conclusions Higher exposure to early life NRAP increased the rate of change of childhood BMI and resulted in a higher attained BMI at age 10 years that were independent of later childhood exposures. These findings suggest that elevated early life NRAP exposures contribute to increased obesity risk in children. Electronic supplementary material The online version of this article (10.1186/s12940-018-0409-7) contains supplementary material, which is available to authorized users.

International recommendations and regulations require developing of National Radon Action Plans (NRAPs) to effectively manage the protection of workers and population from radon exposure. In Italy, a NRAP was published in 2002 and several activities have been carried out in this framework. Information and data regarding these and previous activities have been collected in a National Radon Archive (NRA). Activities carried out by institutionally involved institutes and agencies include several national and regional surveys, involving more than 50 000 indoor environments (dwellings, schools and workplaces), and remedial actions performed in ~350 buildings, largely in schools. Data collected in the NRA allowed also to estimate that lung cancer deaths attributable to radon exposure in Italy are ~3400 per year. On-going developments of the Italian NRA finalized to effectively use it as tool for developing, monitoring and updating the NRAP are also described.

As geologic CO2 storage (GCS) moves towards industrial-scale deployment, strategies must be developed to ensure long-term environmental risks related to potential leakage are managed. One approach to is to perform risk-based subsurface monitoring targeting early leak detection. Early detection is particularly important to address the risk associated with leakage along legacy wells. The challenge in risk-based monitoring is that leakage impacts are expected to be small in comparison with the footprint of the stored CO2 plume and could occur over considerable depths, ranging from the storage formation up to surficial aquifers. Here we demonstrate the application workflow of two of the National Risk Assessment Partnership’s (NRAP) computational tools, WLAT (Wellbore Leakage Analysis Tool) and DREAM (Designs for Risk Evaluation and Management), to a hypothetical CO2 storage site based on a study area in the Midwestern United States. By incorporating site specific wellbore integrity analyses, results show how fluid leakage may be estimated, evaluated, and monitored in terms of risk. For the selected site, three monitoring wells were ultimately needed to detect all possible CO2 leaks and six monitoring wells were needed to minimize time to leak detection. Such analyses inform stakeholders about long-term liability and monitoring costs of GCS projects.

Modeling was conducted to assess the effectiveness of the NRAP toolset, specifically NRAP-Open-IAM and DREAM, to determine a risk-based PISC period and optimized monitoring network for a commercial-scale CO2 storage project. Realizations from NRAP-Open-IAM revealed that maximum simulated leakage rates of brine were small, on the order of 10−5 kg/s, and maximum simulated leakage rates of CO2 were on the order of 10-3 kg/s, and could be detected earliest during the injection phase in the Ironton-Galesville, the thief zone immediately overlying the injection reservoir. Using this information to design an optimized monitoring well network eliminated one of the three originally planned monitoring wells, resulting in a cost reduction for the project. Perhaps the most significant finding from this effort is that NRAP-Open-IAM can be used to define a risk-based, and substantially shorter, PISC period for the site. NRAP-Open-IAM realizations indicate that the majority of risk of endangerment to USDWs decreases within the first 5 years after CO2 injection ends. Doubling this timeframe would still lead to a net PISC period reduction of 40-years and an operational cost reduction in excess of $50 M for the project. This study serves as a first-of-its-kind effort to apply NRAP tools to evaluate components of a commercial-scale Class VI UIC permit and provides a foundation for broader application and adoption by the CCS community.

Background: Air pollution exposure has been shown to increase the risk of obesity and metabolic dysfunction in animal models and human studies. However, the metabolic pathways altered by air pollution exposure are unclear, especially in adolescents and young adults who are at a critical period in the development of cardio-metabolic diseases. Objectives: The aim of this study was to examine the associations between air pollution exposure and indices of fatty acid and amino acid metabolism. Methods: A total of 173 young adults (18–23 years) from eight Children's Health Study (CHS) Southern California communities were examined from 2014 to 2018. Near-roadway air pollution (NRAP) exposure (freeway and non-freeway) and regional air pollution exposure (nitrogen dioxide, ozone and particulate matter) during one year before the study visit were estimated based on participants' residential addresses. Serum concentrations of 64 targeted metabolites including amino acids, acylcarnitines, non-esterified fatty acid (NEFA) and glycerol were measured in fasting serum samples. Principal component analysis of metabolites was performed to identify metabolite clusters that represent key metabolic pathways. Mixed effects models were used to analyze the associations of air pollution exposure with metabolomic principal component (PC) scores and individual metabolite concentrations adjusting for potential confounders. Results: Higher lagged one-year averaged non-freeway NRAP exposure was associated with higher concentrations of NEFA oxidation byproducts and higher NEFA-related PC score (all p's ≤ 0.038). The effect sizes were larger among obese individuals (interaction p = 0.047). Among females, higher freeway NRAP exposure was also associated with a higher NEFA-related PC score (p = 0.042). Among all participants, higher freeway NRAP exposure was associated with a lower PC score for lower concentrations of short- and median-chain acylcarnitines (p = 0.044). Conclusions: Results of this study indicate that NRAP exposure is associated with altered fatty acid metabolism, which could contribute to the metabolic perturbation in obese youth. Keywords: Traffic, Air pollution, Obesity, Metabolic diseases, Metabolomics

Exposure to man-made combustion products, including secondhand tobacco smoke, maternal smoking during pregnancy, and near-roadway air pollution (NRAP), have been associated with increased body mass index and obesity in children and have been shown to result in excess weight gain in animal models. Potential mechanisms include pro-inflammatory central nervous system effects of airborne particles on appetite control, resulting in increased caloric intake, or changes in basal metabolism due to effects on mitochondria and brown adipose tissue. Combustion-derived polyaromatic hydrocarbons have also been linked to altered lipid metabolism, epigenetic effects on PPARγ expression, particle-induced estrogenic effects, and alterations in the distribution of visceral fat. Emerging evidence that a broad spectrum of environmental chemicals have “obesogenic” properties and alter the metabolic profile of adipose tissue challenges the prevailing model that the childhood obesity epidemic is explained solely by increased caloric density of food and decreased physical activity. Research on environmental obesogens could identify novel targets for intervention and yield public health benefits, since NRAP and SHS exposure are both common in populations most at-risk for development of obesity.

The National Risk Assessment Partnership (NRAP) is a research organization focused on developing methods and tools for long-term quantitative risk assessment for carbon storage. NRAP's approach is to divide the carbon storage system into components—reservoir, wells, seals, groundwater, atmosphere—and to develop reduced order models for each of these components. These rapid performance models are trained and/or validated against full physics reservoir models (e.g., TOUGH2, GEM) so that they reproduce similar results but in a fraction of the time of the reservoir model. The different component models can then be combined in an integrated assessment model that can simulate the full system in a matter of seconds or minutes rather than the days, weeks, or longer that a full physics simulation of the entire system would take. The integrated model can then be run in a Monte Carlo mode to assess the probability of failure of a carbon storage system. In NRAP, part of the focus is on long-term leakage risk, and the rapid performance reservoir models are designed to generate pressures and saturations within the reservoir, and particularly at the reservoir-seal interface, both during injection and for up to 1,000 years post injection. These pressures and saturations can then be used as inputs to wellbore or seal leakage models to predict rates and volumes of leakage of CO 2 and/or in situ fluids. In the past few years, NRAP researchers have developed and applied a number of different reduced order models to saline-, gas-, and oil- bearing storage fields. These models vary significantly in several respects. They range from lookup tables or response surfaces to models such as polynomial chaos expansion to models that rely on data mining and artificial intelligence techniques. Each of these types of rapid performance models has different strengths and weaknesses, depending on the method used, the reservoir type, and the goals. In all cases, the rapid performance models required a geologic model and at least some traditional reservoir simulation runs for training or validation purposes. Also, in all techniques developed, an initial analysis is performed to reduce the number of input parameters and scenarios needed for the final simulations. The number of reservoir simulation runs needed can vary significantly based on the reduced order model used. The time and sophistication that it takes to develop a reduced order model is another major factor that varies among the different types of models. Some models are easily able to handle a significant number of varying spatial inputs, while others are limited in the number of input parameters available. Additionally, while all of the rapid performance models will run much faster than a reservoir model, there run times can vary from fractions of a second to tens of seconds or longer, depending on the situation being modeled. This paper will describe the different types of reduced order reservoir models used within NRAP. It will also provide a critical assessment of these rapid performance models, discuss under what circumstances different rapid performance models would be most effective, and evaluate their utility in the context of quantitative risk assessment.

Risk assessment for geologic CO2 storage including quantification of risks is an area of active investigation. The National Risk Assessment Partnership (NRAP) is a US-Department of Energy (US-DOE) effort focused on developing a defensible, science-based methodology and platform for quantifying risk profiles at geologic CO2 sequestration sites. NRAP has been developing a methodology that centers round development of an integrated assessment model (IAM) using system modeling approach to quantify risks and risk profiles. The IAM has been used to calculate risk profiles with a few key potential impacts due to potential CO2 and brine leakage. The simulation results are also used to determine long-term storage security relationships and compare the long-term storage effectiveness to IPCC storage permanence goal. Additionally, we also demonstrate application of IAM for uncertainty quantification in order to determine parameters to which the uncertainty in model results is most sensitive.

The U.S. Department of Energy's (DOE's) National Risk Assessment Partnership (NRAP) Project is developing reduced-order models to evaluate potential impacts on underground sources of drinking water (USDWs) if CO2 or brine leaks from deep CO2 storage reservoirs. Threshold values, below which there would be no predicted impacts, were determined for portions of two aquifer systems. These threshold values were calculated using an interwell approach for determining background groundwater concentrations that is an adaptation of methods described in the U.S. Environmental Protection Agency's Unified Guidance for Statistical Analysis of Groundwater Monitoring Data at RCRA Facilities [1].

Background Emerging evidence indicates that the near-roadway air pollution (NRAP) mixture contributes to CHD, yet few studies have evaluated the associated costs. Objective We integrated an assessment of NRAP-attributable CHD in Southern California with new methods to value the associated mortality and hospitalizations. Methods Based on population-weighted residential exposure to NRAP (traffic density, proximity to a major roadway and elemental carbon), we estimated the inflation-adjusted value of NRAP-attributable mortality and costs of hospitalizations that occurred in 2008. We also estimated anticipated costs in 2035 based on projected changes in population and in NRAP exposure associated with California's plans to reduce greenhouse gas emissions. For comparison, we estimated the value of CHD mortality attributable to PM less than 2.5 μm in diameter (PM 2.5 ) in both 2008 and 2035. Results The value of CHD mortality attributable to NRAP in 2008 was between $3.8 and $11.5 billion, 23% (major roadway proximity) to 68% (traffic density) of the $16.8 billion attributable to regulated regional PM 2.5 . NRAP-attributable costs were projected to increase to $10.6 to $22 billion in 2035, depending on the NRAP metric. Cost of NRAP-attributable hospitalizations for CHD in 2008 was $48.6 million and was projected to increase to $51.4 million in 2035. Conclusions We developed an economic framework that can be used to estimate the benefits of regulations to improve air quality. CHD attributable to NRAP has a large economic impact that is expected to increase by 2035, largely due to an aging population. PM 2.5 -attributable costs may underestimate total value of air pollution-attributable CHD.

The genetic background of dilated cardiomyopathy is highly heterogeneous, with close to 100 known genes and a number of candidates described to date. Nebulin-related-anchoring protein (NRAP) is an actin-binding cytoskeletal protein expressed predominantly in striated and cardiac muscles, and is involved in myofibrillar assembly in the foetal heart and in force transmission in the adult heart. The homozygous NRAP truncating variant (rs201084642), which is predicted to introduce premature stop codon into all NRAP isoforms, was revealed in the dilated cardiomyopathy patient using whole exome sequencing. The same genotype was detected in the asymptomatic proband’s brother. The expression of the NRAP protein was undetectable in the patient’s heart muscle by the Western blot. Genotyping for rs201084642 in the ethnically matched cohort of 231 dilated cardiomyopathy patients did not reveal any additional subjects with this variant. Our findings suggest that the biallelic loss-of-function mutation in NRAP could constitute a relatively rare, low-penetrance genetic risk factor for dilated cardiomyopathy.

© 2016 Elsevier Ltd The US DOE-funded National Risk Assessment Partnership (NRAP) has developed an integrated assessment model (NRAP-IAM-CS) that can be used to simulate carbon dioxide (CO2) injection, migration, and associated impacts at a geologic carbon storage site. The model, NRAP-IAM-CS, incorporates a system-modeling-based approach while taking into account the full subsurface system from the storage reservoir to groundwater aquifers and the atmosphere. The approach utilizes reduced order models (ROMs) that allow fast computations of entire system performance even for periods of hundreds to thousands of years. The ROMs are run in Monte Carlo mode allowing estimation of uncertainties of the entire system without requiring long computational times. The NRAP-IAM-CS incorporates ROMs that realistically represent several key processes and properties of storage reservoirs, wells, seals, and groundwater aquifers. Results from the NRAP-IAM-CS model are used to quantify risk profiles for selected parameter distributions of reservoir properties, seal properties, numbers of wells, well properties, thief zones, and groundwater aquifer properties. A series of examples is used to illustrate how the risk under different storage conditions evolves over time, both during injection, in the near-term post injection period, and over the long term. It is also shown how results from NRAP-IAM-CS can be used to investigate the importance of different parameters on risk of leakage and risk of groundwater contamination under different storage conditions.