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BACKGROUND: Smokers manifest varied phenotypes of pulmonary impairment. RESEARCH QUESTION: Which pulmonary phenotypes are associated with coronary artery disease (CAD) in smokers? STUDY DESIGN AND METHODS: We analyzed data from the University of Pittsburgh COPD Specialized Center for Clinically Oriented Research (SCCOR) cohort (n = 481) and the Genetic Epidemiology of COPD (COPDGene) cohort (n = 2,580). Participants were current and former smokers with > 10 pack-years of tobacco exposure. Data from the two cohorts were analyzed separately because of methodologic differences. Lung hyperinflation was assessed by plethysmography in the SCCOR cohort and by inspiratory and expiratory CT scan lung volumes in the COPDGene cohort. Subclinical CAD was assessed as the coronary artery calcium score, whereas clinical CAD was defined as a self-reported history of CAD or myocardial infarction (MI). Analyses were performed in all smokers and then repeated in those with airflow obstruction (FEV(1) to FVC ratio, < 0.70). RESULTS: Pulmonary phenotypes, including airflow limitation, emphysema, lung hyperinflation, diffusion capacity, and radiographic measures of airway remodeling, showed weak to moderate correlations (r < 0.7) with each other. In multivariate models adjusted for pulmonary phenotypes and CAD risk factors, lung hyperinflation was the only phenotype associated with calcium score, history of clinical CAD, or history of MI (per 0.2 higher expiratory and inspiratory CT scan lung volume; coronary calcium: OR, 1.2; 95% CI, 1.1-1.5; P = .02; clinical CAD: OR, 1.6; 95% CI, 1.1-2.3; P = .01; and MI in COPDGene: OR, 1.7; 95% CI, 1.0-2.8; P = .05). FEV(1) and emphysema were associated with increased risk of CAD (P < .05) in models adjusted for CAD risk factors; however, these associations were attenuated on adjusting for lung hyperinflation. Results were the same in those with airflow obstruction and were present in both cohorts. INTERPRETATION: Lung hyperinflation is associated strongly with clinical and subclinical CAD in smokers, including those with airflow obstruction. After lung hyperinflation was accounted for, FEV(1) and emphysema no longer were associated with CAD. Subsequent studies should consider measuring lung hyperinflation and examining its mechanistic role in CAD in current and former smokers.

RATIONALE: Multiple studies have demonstrated an increased risk of chronic obstructive pulmonary disease (COPD) in heterozygous carriers of the AAT (alpha-1 antitrypsin) Z allele. However, it is not known if MZ subjects with COPD are phenotypically different from noncarriers (MM genotype) with COPD. OBJECTIVES: To assess if MZ subjects with COPD have different clinical features compared with MM subjects with COPD. METHODS: Genotypes of SERPINA1 were ascertained by using whole-genome sequencing data in three independent studies. We compared outcomes between MM subjects with COPD and MZ subjects with COPD in each study and combined the results in a meta-analysis. We performed longitudinal and survival analyses to compare outcomes in MM and MZ subjects with COPD over time. MEASUREMENTS AND MAIN RESULTS: We included 290 MZ subjects with COPD and 6,184 MM subjects with COPD across the three studies. MZ subjects had a lower FEV(1)% predicted and greater quantitative emphysema on chest computed tomography scans compared with MM subjects. In a meta-analysis, the FEV(1) was 3.9% lower (95% confidence interval [CI], −6.55% to −1.26%) and emphysema (the percentage of lung attenuation areas

Background Attenuation of transforming growth factor β by blocking angiotensin II has been shown to reduce emphysema in a murine model. General population studies have demonstrated that the use of angiotensin converting enzyme inhibitors (ACEis) and angiotensin-receptor blockers (ARBs) is associated with reduction of emphysema progression in former smokers and that the use of ACEis is associated with reduction of FEV1 progression in current smokers. Research Question Is use of ACEi and ARB associated with less progression of emphysema and FEV1 decline among individuals with COPD or baseline emphysema? Methods Former and current smokers from the Genetic Epidemiology of COPD Study who attended baseline and 5-year follow-up visits, did not change smoking status, and underwent chest CT imaging were included. Adjusted linear mixed models were used to evaluate progression of adjusted lung density (ALD), percent emphysema (%total lung volume Results Over 5 years of follow-up, compared with nonusers, ACEi and ARB users with COPD showed slower ALD progression (adjusted mean difference [aMD], 1.6; 95% CI, 0.34-2.9). Slowed lung function decline was not observed based on phase 1 medication (aMD of FEV1 % predicted, 0.83; 95% CI, –0.62 to 2.3), but was when analysis was limited to consistent ACEi and ARB users (aMD of FEV1 % predicted, 1.9; 95% CI, 0.14-3.6). No effect modification by smoking status was found for radiographic outcomes, and the lung function effect was more pronounced in former smokers. Results were similar among participants with baseline emphysema. Interpretation Among participants with spirometry-confirmed COPD or baseline emphysema, ACEi and ARB use was associated with slower progression of emphysema and lung function decline. Trial Registry ClinicalTrials.gov ; No.: NCT00608764; URL: www.clinicaltrials.gov

Rationale: Increasing awareness of the prevalence and significance of Preserved Ratio Impaired Spirometry (PRISm), alternatively known as restrictive or Global Initiative for Chronic Obstructive Lu...

Contains fulltext : 194255.pdf (Publisher’s version ) (Open Access) BACKGROUND: Emphysema has considerable variability in its regional distribution. Craniocaudal emphysema distribution is an important predictor of the response to lung volume reduction. However, there is little consensus regarding how to define upper lobe-predominant and lower lobe-predominant emphysema subtypes. Consequently, the clinical and genetic associations with these subtypes are poorly characterized. METHODS: We sought to identify subgroups characterized by upper-lobe or lower-lobe emphysema predominance and comparable amounts of total emphysema by analyzing data from 9,210 smokers without alpha-1-antitrypsin deficiency in the Genetic Epidemiology of COPD (COPDGene) cohort. CT densitometric emphysema was measured in each lung lobe. Random forest clustering was applied to lobar emphysema variables after regressing out the effects of total emphysema. Clusters were tested for association with clinical and imaging outcomes at baseline and at 5-year follow-up. Their associations with genetic variants were also compared. RESULTS: Three clusters were identified: minimal emphysema (n = 1,312), upper lobe-predominant emphysema (n = 905), and lower lobe-predominant emphysema (n = 796). Despite a similar amount of total emphysema, the lower-lobe group had more severe airflow obstruction at baseline and higher rates of metabolic syndrome compared with subjects with upper-lobe predominance. The group with upper-lobe predominance had greater 5-year progression of emphysema, gas trapping, and dyspnea. Differential associations with known COPD genetic risk variants were noted. CONCLUSIONS: Subgroups of smokers defined by upper-lobe or lower-lobe emphysema predominance exhibit different functional and radiological disease progression rates, and the upper-lobe predominant subtype shows evidence of association with known COPD genetic risk variants. These subgroups may be useful in the development of personalized treatments for COPD.

Rationale: The American Thoracic Society (ATS)/European Respiratory Society defines a positive bronchodilator response (BDR) by a composite of BDR in either forced expiratory volume in 1 second (FEV(1)) and/or forced vital capacity (FVC) greater than or equal to 12% and 200 ml (ATS-BDR). We hypothesized that ATS-BDR components would be differentially associated with important chronic obstructive pulmonary disease (COPD) outcomes. Objectives: To examine whether ATS-BDR components are differentially associated with clinical, functional, and radiographic features in COPD. Methods: We included subjects with COPD enrolled in the COPDGene study. In the main analysis, we excluded subjects with self-reported asthma. We categorized BDR into the following: 1) No-BDR, no BDR in either FEV(1) or FVC; 2) FEV(1)-BDR, BDR in FEV(1) but no BDR in FVC; 3) FVC-BDR, BDR in FVC but no BDR in FEV(1); and 4) Combined-BDR, BDR in both FEV(1) and FVC. We constructed multivariable logistic, linear, zero-inflated negative binomial, and Cox hazards models to examine the association of BDR categories with symptoms, computed tomography findings, change in FEV(1) over time, respiratory exacerbations, and mortality. We also created models using the ATS BDR definition (ATS-BDR) as the main independent variable. Results: Of 3,340 COPD subjects included in the analysis, 1,083 (32.43%) had ATS-BDR, 182 (5.45%) had FEV(1)-BDR, 522 (15.63%) had FVC-BDR, and 379 (11.34%) had Combined-BDR. All BDR categories were associated with FEV(1) decline compared with No-BDR. Compared with No-BDR, both ATS-BDR and Combined-BDR were associated with higher functional residual capacity %predicted, greater internal perimeter of 10 mm, and greater 6-minute-walk distance. In contrast to ATS-BDR, Combined-BDR was independently associated with less emphysema (adjusted beta regression coefficient, −1.67; 95% confidence interval [CI], −2.68 to −0.65; P = 0.001), more frequent respiratory exacerbations (incidence rate ratio, 1.25; 95% CI, 1.03–1.50; P = 0.02) and severe exacerbations (incidence rate ratio, 1.34; 95% CI, 1.05–1.71; P = 0.02), and lower mortality (adjusted hazards ratio, 0.76; 95% CI, 0.58–0.99; P = 0.046). Sensitivity analysis that included subjects with self-reported history of asthma showed similar findings. Conclusions: BDR in both FEV(1) and FVC indicates a COPD phenotype with asthma-like characteristics, and provides clinically more meaningful information than current definitions of BDR.

The notion of reducing our environmental footprint, minimizing leaks and spillages, and identifying operational efficiencies is nothing new. We have been addressing these issues for years. Sustainability, however, has gained a higher profile recently, especially since the 2015 United Nations Framework Convention on Climate Change accord and the evolution of alternative energies. It came, therefore, as a pleasant surprise to review an extraordinary wealth of well-written papers relating not only to this topic, but to all manner of fascinating engineering issues. Let me back up a bit. For 6 years, I have provided commentary concerning matters relating to reservoir simulation. This was often illuminating, but my primary interest has always been in full-field modeling: coupling our models for flow in porous media, wellbore, network, and to facilities. I firmly believe that unified full-field modeling can furnish benefits both operationally and economically. In accepting the challenge to write this, however, I did not expect to encounter the extraordinary breadth of topics covered. Saying that, one clear thread did emerge from the articles reviewed - namely reliability, emissions control, and energy saving and monitoring, all of which relate to sustainability in one way or another. Novel methods for valve- failure prediction, pipeline coatings, floating storage tank roof optimization, and the use of drones (from spray painting to surveillance) along with robots for unmanned installations were all topics represented in the papers provided me. Paper SPE 198165 is an informative overview of alternative fuels and how these may affect Middle East production; however, this should appeal to a wider readership because it reviews alternative energies nicely. Paper IPTC 19775 provides a means to better quantify separator shrinkage, which can result in errors in stock-tank rates up to 20% (essential if one is to quantify unit energy consumption accurately). Paper SPE 197759 proposes methods for energy savings. These papers represent but a small sample of a broader swath of articles from the past year relating to this catch-all term “sustainability.” Recommended additional reading at OnePetro: www.onepetro.org. SPE 197753 Parametric Study on Wind Fatigue Life of Long Span Flare-Boom Based on Directional Input Parameters to Harris Wind Spectra and Selection of Wind Blocks by Sachin Samant, National Petroleum Construction Company, et al. SPE 198133 Internal Corrosion Severity Ranking of Crude Oil Pipelines by Amer Jaragh, Kuwait Oil Company, et al. SPE 197620 Ground Robotics Enabler for Normally Unattended Installations by Jean-Michel Munoz, Total, et al.

Background Chronic bronchitis (CB) increases risk of COPD exacerbations. We have shown that the St. George's Respiratory Questionnaire (SGRQ) CB definition identifies patients with a similar clinical phenotype as classically defined CB. Whether the SGRQ CB definition is a predictor of future COPD exacerbations is unknown. Methods We analyzed 7,557 smokers with normal spirometry and Global Initiative for Chronic Obstructive Lung Disease stage 1-4 COPD in the Genetic Epidemiology of COPD study with longitudinal follow-up data on exacerbations. Subjects were divided into classic CB+ or classic CB–, using the classic definition. In addition, subjects were divided into SGRQ CB+ or SGRQ CB–. Exacerbation frequency and severe exacerbation frequency were determined in each group. Multivariable linear regressions were performed for exacerbation frequency with either classic CB or SGRQ CB and relevant covariates. Results There were 1,434 classic CB+ subjects and 2,290 SGRQ CB+ subjects. The classic CB+ group had a greater exacerbation frequency compared with the classic CB– group (0.69 ± 1.26 vs 0.36 ± 0.90 exacerbations per patient per year; P Conclusions The SGRQ CB definition identified more subjects at risk for future exacerbations than the classic CB definition. SGRQ CB was at least a similar if not better predictor of future exacerbations than classic CB.

Spirometric Volumes and Breathlessness Across Levels of Airflow Limitation : The COPDGene Study.

BACKGROUND:Eosinophilic airway inflammation in patients with chronic obstructive pulmonary disease (COPD) is associated with exacerbations and responsivity to steroids, suggesting potential shared mechanisms with eosinophilic asthma. However, there is no consistent blood eosinophil count that has been used to define the increased exacerbation risk. OBJECTIVE:We sought to investigate blood eosinophil counts associated with exacerbation risk in patients with COPD. METHODS:Blood eosinophil counts and exacerbation risk were analyzed in patients with moderate-to-severe COPD by using 2 independent studies of former and current smokers with longitudinal data. The Genetic Epidemiology of COPD (COPDGene) study was analyzed for discovery (n=1,553), and the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study was analyzed for validation (n=1,895). Asubset of the ECLIPSE study subjects were used to assess the stability of blood eosinophil counts over time. RESULTS:COPD exacerbation risk increased with higher eosinophil counts. An eosinophil count threshold of 300cells/μL or greater showed adjusted incidence rate ratios for exacerbations of 1.32 in the COPDGene study (95% CI, 1.10-1.63). The cutoff of 300cells/μL or greater was validated for prospective risk of exacerbation in the ECLIPSE study, with adjusted incidence rate ratios of 1.22 (95% CI, 1.06-1.41) using 3-year follow-up data. Stratified analysis confirmed that the increased exacerbation risk associated with an eosinophil count of 300cells/μL or greater was driven by subjects with a history of frequent exacerbations in both the COPDGene and ECLIPSE studies. CONCLUSIONS:Patients with moderate-to-severe COPD and blood eosinophil counts of 300cells/μL or greater had an increased risk exacerbations in the COPDGene study, which was prospectively validated in the ECLIPSE study.

The heritability of chronic obstructive pulmonary disease (COPD) cannot be fully explained by recognized genetic risk factors identified as achieving genome-wide significance. In addition, the combined contribution of genetic variation to COPD risk has not been fully explored. We sought to determine: (1) whether studies of variants from previous studies of COPD or lung function in a larger sample could identify additional associated variants, particularly for severe COPD; and (2) the impact of genetic risk scores on COPD. We genotyped 3,346 single-nucleotide polymorphisms (SNPs) in 2,588 cases (1,803 severe COPD) and 1,782 control subjects from four cohorts, and performed association testing with COPD, combining these results with existing genotyping data from 6,633 cases (3,497 severe COPD) and 5,704 control subjects. In addition, we developed genetic risk scores from SNPs associated with lung function and COPD and tested their discriminatory power for COPD-related measures. We identified significant associations between SNPs near PPIC (P = 1.28 X 10(-8)) and PPP4R4/SERPINA1 (P = 1.01 X 10(-8)) and severe COPD; the latter association may be driven by recognized variants in SERPINA1. Genetic risk scores based on SNPs previously associated with COPD and lung function had a modest ability to discriminate COPD (area under the curve, similar to 0.6), and accounted for a mean 0.9-1.9% lower forced expiratory volume in 1 second percent predicted for each additional risk allele. In a large genetic association analysis, we identified associations with severe COPD near PPIC and SERPINA1. A risk score based on combining genetic variants had modest, but significant, effects on risk of COPD and lung function.

Background: Beta-blockers are commonly prescribed for patients with cardiovascular disease. Providers have been wary of treating chronic obstructive pulmonary disease (COPD) patients with beta-blockers due to concern for bronchospasm, but retrospective studies have shown that cardio-selective beta-blockers are safe in COPD and possibly beneficial. However, these benefits may reflect symptom improvements due to the cardiac effects of the medication. The purpose of this study is to evaluate associations between beta-blocker use and both exacerbation rates and longitudinal measures of lung function in two well-characterized COPD cohorts. Methods: We retrospectively analyzed 1219 participants with over 180 days of follow up from the STATCOPE trial, which excluded most cardiac comorbidities, and from the placebo arm of the MACRO trial. Primary endpoints were exacerbation rates per person-year and change in spirometry over time in association with beta blocker use. Results: Overall 13.9% (170/1219) of participants reported taking beta-blockers at enrollment. We found no statistically significant differences in exacerbation rates with respect to beta-blocker use regardless of the prevalence of cardiac comorbidities. In the MACRO cohort, patients taking beta-blockers had an exacerbation rate of 1.72/person-year versus a rate of 1.71/person-year in patients not taking beta-blockers. In the STATCOPE cohort, patients taking beta-blockers had an exacerbation rate of 1.14/person-year. Patients without beta-blockers had an exacerbation rate of 1.34/person-year. We found no detrimental effect of beta blockers with respect to change in lung function over time. Conclusion: We found no evidence that beta-blocker use was unsafe or associated with worse pulmonary outcomes in study participants with moderate to severe COPD.

Technology Focus A radical digital revolution is happening all around us (or so we are told). This digital domain is moving so rapidly that new acronyms are being added to our lexicon almost weekly (BD, DA, DNN, GAN, and ML, to name but a few). So how will this affect reservoir simulation? Speaking for myself, I really do not know. However, I came across an interesting article from the Harvard Business Review that examined the effect of innovative information technology (IIT) on some large US-based consumer businesses, and, while specific benefits of IIT were clearly stated, the authors opined, “In times of radical technological change, there’s a lot of figuring out to do. [We] have to understand what new technologies can do.” Applying this to reservoir simulation, we apparently need to understand better when and, more importantly, when not to use such technology—to appreciate its bounds, its limitations, its range of validity, and so on. Deep neural networks (DNNs), for example, are excellent at labeling images (cat, dog, axolotl, etc.). However, some futurists have an impression that IIT can solve almost any kind of problem, sometimes leading to extravagant claims about its potential utility. Futurists are optimists in nature (the ones I have seen certainly are). However, such buoyant proclamations require some counterbalance through honest questions, healthy discussion, and a reluctance to accept such bold assertions as dogma. Without wishing to appear too skeptical, I came across an article from The Royal Society that is well worth quoting directly: “No matter their ‘depth’ and the sophistication of data-driven methods, in the end, they merely fit curves to existing data. Not only do these methods invariably require far larger quantities of data than anticipated … they can also fail in circumstances beyond the range of the data used to train them because they are not designed to model the structural characteristics of the underlying system.” While this article focuses on biology and medicine, the authors apply their keen insight to any multiscale and complex system, which covers our domain of interest. I feel that a tempered, modestly restrained approach to IIT is indeed wise (as applied to reservoir simulation), at least until we have had time to fathom where this digital revolution is leading. Recommended additional reading at OnePetro: www.onepetro.org. SPE 186079 Implicit Modeling for Permeability Enhancement in Carbonate Reservoirs: A Novel Approach To Bridge Data Gaps for Honoring Dynamic Observations by Arthur P.C. Lavenu, Abu Dhabi Marine Operating Company, et al. SPE 187046 Integrated Reservoir-Network Simulation Improves Modeling and Selection of Subsea Boosting Systems for a Deepwater Development by Gaurav Seth, Chevron, et al. SPE 187453 Assessing Single EOS Predictability Using PVT Properties of a Wet-Gas Reservoir on a Compositional Simulator by Bander N. Al Ghamdi, Saudi Aramco, et al.

Background Randomized trials have demonstrated benefits of biventricular (BiV) pacing in patients with advanced heart failure, intraventricular conduction delay, and atrial fibrillation (AF) postatrioventricular (AV) node ablation. The AV Node Ablation with CLS and CRT Pacing Therapies for Treatment of AF trial (AVAIL CLS/CRT) was designed to demonstrate superiority of BiV pacing in patients with AF after AV node ablation, to evaluate its effects on cardiac structure and function, and to investigate additional benefits of Closed Loop Stimulation ® (CLS) (BIOTRONIK, Berlin, Germany). Methods Patients with refractory AF underwent AV node ablation and were randomized (2:2:1) to BiV pacing with CLS, BiV pacing with accelerometer, or right ventricular (RV) pacing. Echocardiography was performed at baseline and 6 months, with paired data available for 108 patients. Results The RV pacing contributed to significant increase in left atrial volume, left ventricular (LV) end-systolic volume, and LV mass compared to BiV pacing. Ejection fraction decreased insignificantly with RV pacing compared to significant increase with BiV pacing. Interventricular dyssynchrony significantly decreased with BiV compared with RV pacing. Closed Loop Stimulation ® did not result in additional echocardiographic changes; heart rate distribution was significantly wider with CLS. All groups showed significant improvement in 6-minute walk distance, quality-of-life score, and New York Heart Association class. Conclusion In conclusion, RV pacing results in significant increase in left atrial volume, LV mass, and worsening of LV contractility compared to patients receiving BiV pacing post-AV node ablation for refractory AF. Closed Loop Stimulation ® was not associated with additional structural changes but resulted in significantly wider heart rate distribution.

Purpose Adverse reaction rates to gadolinium based magnetic resonance imaging (MRI) contrast agents which occur immediately post-injection are well documented. However little research has investigated delayed reaction rates (i.e. 30 min–24 h). This study evaluated the rate of immediate and delayed adverse reaction rates to a gadolinium based MRI contrast agent (Dotarem®) and investigated the effect of a hydration regime on the rate of adverse events. Method Fifty-eight patients received no preparation, prior to administration of the contrast agent, whilst another 58 underwent a hydration protocol. The patients had their answers to a questionnaire recorded immediately after the scanning procedure and also via a follow-up telephone call 24 h later. Results In the unprepared group 9 patients (15.5%) experienced immediate adverse events, i.e. within 0–30 min, whereas 24 (41.4%) experienced delayed reactions (30 min–24 h) after administration of the contrast agent. In the hydrated patient group 6 (10.3%) experienced an immediate adverse event, whilst 8 (13.7%) experienced delayed events post-injection. The difference in the total reaction rates for the unprepared and hydrated groups was statistically significant for immediate and delayed reactions. The difference in the rates of delayed headache, nausea, dizziness and problems with the injection site, for the unprepared and hydrated groups was statistically significant. Conclusion An oral hydration regime administered to patients, both before and after MRI contrast agent administration significantly reduced the total number of immediate and delayed reactions. It also significantly reduced delayed headache, nausea, dizziness and problems at the injection site. Whilst this pilot study had methodological shortcomings, the strength of the relationship demonstrated are worthy of further investigation.

A 13-year-old male with a previous one-month history of a ‘locking’ painful knee underwent an MR investigation of his knee. The MR findings showed a discoid meniscus with a meniscal tear, which at arthroscopy proved to be an unusual Wrisberg III variant. The morphology of discoid meniscus is defined including the Wrisberg III variant. The MR factors are discussed including optimum planes and sequences used by MRI to investigate meniscal pathologies including tears. The treatment regimes are investigated including surgical options.

The American Journal of Neuro-Radiology (AJNR) has produced a framework and guidelines for the reporting of the Lumbar spine in Magnetic Resonance Imaging. These guidelines have provided a universally acceptable nomenclature that is simple and gives a system of classifications and reporting built upon that nomenclature. Some of the main proposals and definitions of the AJNR recommendations are discussed with the aid of both schematic and MR images including degenerative pathologies of the lumbar spine to further simplify the guidelines.

This study was designed to determine the flexibility that selected principals preferred when implementing financial site-based decision making in their schools. To complete the research, the fund categories representing areas of educational functions and service in the school system chart of accounts were evaluated. The findings indicated that principals have a strong desire to gain control over the funds they feel will help them improve instruction. The principals in the study did not show a desire to revamp the finance process, but desired to have more flexibility in the use of funds associated with instructional programs. Further, the principals revealed they could make significant changes in their educational programs without increas ing the amount of funds in the budget.

Technology Focus Benchmark cases are a good thing. They provide a systematic means to compare processes, technologies, and performance that benefits companies, industry, and research organizations. One notable benchmark was deliberated at a 2008 SPE Applied Technology Workshop in the picturesque Belgium town of Bruges. This particular challenge involved history matching followed by forecast optimization. The goal was to maximize a 20-year net present value (NPV). The results were published as SPE-119094-PA in 2010. The Bruges study has since become the basis of numerous articles and simulation-based studies and continues to be influential to this day. Now, almost 10 years later, a new benchmark challenge has been set: Olympus. This has different, but no less challenging, objectives, and the goal is, once again, to maximize a 20-year NPV subject to some stated constraints. Olympus has been set by Integrated System Approaches for Petroleum Production 2 (ISAPP-2), a research partnership between Delft University of Technology and the Netherlands Organization for Applied Scientific Research (TNO), who originated the original Bruges challenge, along with Eni, Statoil, and Petrobras as industrial partners. For this, we owe a debt of thanks. Issues identified in the original Bruges exercise have been addressed, and a more streamlined benchmarking procedure has been defined. The ambition is no less broad and can be concisely stated as “field-development optimization under uncertainty.” While Olympus has no history-matching component (which formed part of the Bruges challenge), we are now faced with geological uncertainties related to faulting, fault throws, barriers, and channeling. The ensemble of 50 Olympus reservoir models provides such geological uncertainties that we must face when dealing with real field-development planning studies. The participant must decide how many producers and injectors to drill and where to drill them, along with their operational management during a 20-year production forecast. All this, of course, is addressed in the presence of geological uncertainty. One can imagine the results will vary considerably in formulation, ambition, and approach. I hope that this will not be considered a winner-take-all competition because that goes against the spirit of such a benchmark. The reward will ultimately turn out to be increased insight and appreciation of new approaches and techniques that will be shared throughout the industry. So, I humbly request that you consider participating in this challenge. Clear and concise online material is available from the ISAPP-2 website (www.isapp2. com/optimization-challenge), which also instructs you on how to download model files. The gauntlet has been thrown down, and I know that we, as an industry, have the wherewithal to pick it up. Recommended additional reading at OnePetro: www.onepetro.org. SPE 182637 Probabilistic Uncertainty Quantification of a Complex Field Using Advanced Proxy-Based Methods and GPU-Based Reservoir Simulation by N. Goodwin, Essence Products and Services, et al. SPE 181686 Effects of Confined Space on Production From Tight Reservoirs by Brian C. Stimpson, Texas A&M University, et al. SPE 182636 Dynamic Mesh Adaptivity for Immiscible Viscous Fingering by A. Adam, Imperial College London, et al. SPE 182718 A Massively Parallel Semicoarsening Multigrid Linear Solver on Multicore and Multi-GPU Architectures by A.M. Manea, Stanford University, et al. IPTC 18955 Building More-Realistic 3D Facies-Indicator Models by Thomas Le Blévec, Imperial College, et al.

Clostridial infection of the aorta is a rare and life-threatening condition. The management of a mycotic aneurysm involving the thoracoabdominal aorta due to Clostridium septicum infection is presented. Successful surgical management of the aortic infection involved arterial resection, wide debridement of the surrounding tissues, and in situ graft replacement. Sixteen additional cases of clostridial infection of the aortoiliac segment reported in the literature are also summarized. In ten of these 17 cases, an associated colonic adenocarcinoma was documented.

Chronic obstructive pulmonary disease (COPD) is a condition in which continuous bronchodilation may have clinical advantages. This study evaluated salmeterol, a beta-agonist bronchodilator with a duration of action substantially longer than that of short-acting beta-agonists, compared with ipratropium, an anticholinergic bronchodilator, and placebo in patients with COPD. Four hundred and five patients with COPD received either salmeterol 42 microg twice daily, ipratropium bromide 36 microg four times daily, or placebo for 12 wk in this randomized, double-blind, parallel-group study. Patients were stratified on the basis of bronchodilator response to albuterol (12% and200-ml improvement) and were randomized within each stratum. Bronchodilator response was measured over 12 h four times during the treatment period. Salmeterol provided similar maximal bronchodilatation to ipratropium but had a longer duration of action and a more constant bronchodilatory effect with no evidence of bronchodilator tolerance. Both active treatments were well tolerated. Salmeterol was an effective bronchodilator with a consistent effect over this 12-wk study in patients with COPD, including those "unresponsive" to albuterol. The long duration of action of salmeterol offers the advantage of twice daily dosing compared with the required four times a day dosing with ipratropium.

Background —Electrical storm (ES), defined as recurrent multiple ventricular fibrillation (VF) episodes, often occurs in patients with recent myocardial infarction. Because treating ES according to the Advanced Cardiac Life Support (ACLS) guidelines yields a poor outcome, we evaluated the efficacy of sympathetic blockade in treating ES patients and compared their outcome with that of patients treated according to the ACLS guidelines. Methods and Results —Forty-nine patients (36 men, 13 women, mean age 57±10 years) who had ES associated with a recent myocardial infarction were separated into 2 groups. Patients in group 1 (n=27) received sympathetic blockade treatment: 6 left stellate ganglionic blockade, 7 esmolol, and 14 propranolol. Patients in group 2 (n=22) received antiarrhythmic medication as recommended by the ACLS guidelines. Patient characteristics were similar in the 2 groups. The 1-week mortality rate was higher in group 2: 18 (82%) of the 22 patients died, all of refractory VF; 6 (22%) of the 27 group 1 patients died, 3 of refractory VF ( P P Conclusions —Sympathetic blockade is superior to the antiarrhythmic therapy recommended by the ACLS guidelines in treating ES patients. Our study emphasizes the role of increased sympathetic activity in the genesis of ES. Sympathetic blockade−not class 1 antiarrhythmic drugs−should be the treatment of choice for ES.

This study established three fundamental research goals: to determine the degree to which upper class Mexicans have a positive attitude toward foreign made products using the CETSCALE; to ascertain socio-demographic characteristics associated with malinchismo; and to evaluate if malinchismo influences Mexican consumers' purchasing behavior. Using interviews with 400 Mexican consumers, it was determined that upper-income Mexicans prefer foreign products, but this was mediated by age, education, and household size.

In the United Kingdom there is currently no standardisation of nomenclature in the reporting of degenerative disc disease. The present variations in the usage of language are responsible for confusion and controversy. As a result of this, our chances of reaching a consensus on the diagnosis and treatment of disc disorders are compromised. The different terminologies used in reporting degenerative disc disease could give rise to many potential problems and may have major implications on patient treatment and management, NHS resources and potentially litigation. One example of an ambiguous expression would be the use of ‘disc fragment’. This could imply that the disc had separated and produced a sequestrated fragment. Sequestrations are completely free disc fragments, which can roam throughout the thecal sac and can be extremely troublesome to locate during surgery (see Fig. 1). If surgery were to be undertaken the surgeon would need to isolate and remove the ‘sequestration’. For a successful surgical outcome a complete removal of

Large electric power plant generators typically use gaseous hydrogen to remove heat from the generator windings and deliver the heat to the cooling water. Hydrogen is used in a closed cycle, and only a modest amount of makeup hydrogen is used daily to make up for hydrogen losses — typically about 300 to 700 scf/d. The range of hydrogen usage depends on several factors. In addition to hydrogen used for makeup, all power plants using hydrogen-cooled generators must plan for hydrogen supply to re-gas a generator after the generator has been degassed. Typical generator re-gas quantities are in the range of 15× the daily makeup amount, and must be available in a short period of time. Thus a generator which might require 300 to 700 scf of hydrogen over 24 hours for daily makeup may require 4500 to 10,500 scf of hydrogen in just a few hours for re-gas. The re-gas hydrogen is added back to the generator as quickly as the re-gas process allows — typically over 3–5 hours — so that an out-of-service generator can be brought online and producing revenue again. Hydrogen for power plant generator cooling can be supplied either through hydrogen delivered to the plant from a remote source in gaseous or liquid form, or can be made at the plant using an on-site hydrogen generator. Makeup hydrogen and re-gas hydrogen do not necessarily require the same source of hydrogen — because the requirements of re-gas hydrogen are very different from the requirements of makeup hydrogen, it may be more efficient to use two different approaches. On-site hydrogen generation for power plant hydrogen supply is widespread in the developing world, and is beginning to displace delivered hydrogen as the preferred approach in the U.S., Canada and Europe. Outside U.S., Canada and Europe, there may be no delivery infrastructure for hydrogen manufacture and delivery to the plant — a hydrogen-cooled power plant may need to take care of its own hydrogen needs to ensure that the plant can be operated. In the U.S., Canada and Europe hydrogen deliveries are available, but on-site generated hydrogen is gaining acceptance because it reduces costs and operational complexity, and improves safety. This paper will review several cases where on-site hydrogen generation has been used to reduce the cost of design, construction and operation of newly built power plants, both in the U.S., Canada and Europe and in areas where hydrogen is far less available.Copyright © 2013 by ASME

Overview Reservoir-simulation-model inputs are numerous, and uncertainty is pervasive— before, during, and after development. On top of that, there is always pressure to deliver quality results as quickly as possible. This gives rise to a simple question, one that has yet to find a simple answer: How refined is refined enough and how coarse is too coarse? I run the risk of oversimplification here, but it seems we are faced with a classic dichotomy, one that is exacerbated by the pull of advances in high-performance computing that permit ever-greater model refinement, while, simultaneously, we have the push of (possibly stochastic) sampling of uncertainty, thereby encouraging the development of simplified (or surrogate) models that can run hundreds, even thousands, of times. The question is one of striking the right balance between two apparently contradictory approaches to simulation. The adage “horses for courses” is not particularly helpful in itself, even though it is probably appropriate. Does one have two distinct models with roughly commensurate scaling, or can we build a single all-purpose model with different scales within it that is both fast and accurate with multiscale grid? Dimensional scale represents just one aspect of the term “multiscale,” which I have mistakenly taken to mean just the juxtaposition of, essentially, geometrical scale within a single model (such as that found in coupling a simulation grid and the wellbore). The large ratio associated with domain size, and the resolution of the geological data, is usually managed by upscaling. However, so-called multiscale methods represent a new avenue of research, one that may provide a bridge between the aforementioned push and pull of refinement resulting from the needs of different decision makers. Multiscale, which has been the subject of ongoing study over the past decade, knits together geometrical quantities (dimensional scale) with tailored computational schemas (numerical scale). This multifaceted multiscale concept may offer a means to construct an accurate coarser-scaled model, one honoring the attributes of the fine-scale heterogeneous geological data from both numerical and spatial standpoints. This method class computes local basis functions for the solution variables, to construct a smaller (coarse) system for computing an approximate solution on the original simulation grid. While it is too early to say whether this broader notion of multiscale (numerical and geometrical) will provide a single, unifying, model for engineers, it is possible that this, or some other such method, may strike that elusive balance between refinement (accuracy) and surrogacy (speed). For those interested in reading up on this topic, the peer-reviewed SPE papers SPE 119183 and SPE 163649 provide more detail and clarify the status of some ongoing research. JPT Recommended additional reading at OnePetro: www.onepetro.org. SPE 169063 Application of Multiple- Mixing-Cell Method To Improve Speed and Robustness of Compositional Simulation by Mohsen Rezaveisi, The University of Texas at Austin, et al. SPE 177634 Multiscale Geomechanics: How Much Model Complexity Is Enough? by Gerco Hoedeman, Baker Hughes SPE 174905 Experimental Design or Monte Carlo Simulation? Strategies for Building Robust Surrogate Models by Jared Schuetter, Battelle Memorial Institute, et al. SPE 169357 Reduced-Order Modeling in Reservoir Simulation Using the Bilinear Approximation Techniques by Mohammadreza Ghasemi, Texas A&M University, et al.

The effects of moderate, chronic (5 days) potassium depletion on cardiac function were assessed in 14 normokalemic and 13 hypokalemic open chest, anesthetized dogs. Cardiac responses to intravenous bolus injection of 2.5 micrograms/kg body weight epinephrine (10 normokalemic and 11 hypokalemic dogs) and to rapidly increased preload (8 dogs in each group) were evaluated. Hypokalemic dogs received a low potassium diet plus chlorthalidone. Plasma potassium levels were lower (p less than 0.001) in the hypokalemic dogs (3.2 +/- 0.1 mEq/liter [mean +/- SEM]) than in the normokalemic dogs (4.1 +/- 0.1). The inotropic response to epinephrine was lower in hypokalemic than in normokalemic dogs, the response of the maximal rate of rise of left ventricular pressure was 20% greater (p less than 0.03) and the response of the peak rate of change of ejection power was 60% greater in the normokalemic dogs. The relaxation response to epinephrine (the maximal rate of fall of left ventricular pressure) was 33% lower (p less than 0.02) in hypokalemic dogs. Responses to rapid volume expansion were impaired by hypokalemia; maximal stroke volume index was 31% lower (p less than 0.01), maximal cardiac index was 26% lower (p less than 0.01) and the peak response to the maximal rate of filling was 51% lower (p less than 0.01). There were no differences in basal cardiac function. Therefore, modest potassium depletion within the clinical range impaired the contractile and relaxation responses to epinephrine and preload and impaired rapid filling.

Introduction: Of the 10 secretory phospholipase A 2 (sPLA 2 ) enzymes expressed in humans, Group X (GX) sPLA 2 is the most potent in hydrolyzing phospholipids on cell membranes. In addition to its lipolytic activity, GX sPLA 2 is also a high affinity ligand for the M-type sPLA 2 receptor. Although numerous studies have implicated GX sPLA 2 in important biological processes in vitro , data from studies in vivo are lacking. To elucidate the physiological functions of this enzyme we recently developed C57BL/6 mice with targeted deletion of the GX sPLA 2 gene. Results : Analysis by real time RT-PCR showed that GX sPLA 2 mRNA is widely distributed in mouse tissues, with highest expression in intestine, testes, brain, thymus, spleen, fat, lung, and heart. Unlike some of the other members of the sPLA 2 family, tissue expression of GX sPLA 2 was not highly upregulated in mice injected with lipopolysaccharide. However, GX sPLA 2 was induced almost 5-fold in retroperitoneal fat of mice fed a high-fat (60 kcal%) diet for 17 weeks.Targeted disruption of GX sPLA 2 resulted in increased body weight in 1.5 year-old mice fed a normal laboratory diet (male GX sPLA 2 +/+ mice: 35.8±0.4 g; male GX sPLA 2 −/− mice: 45.033.2 g; p2 +/+ mice: 16.0±1.0%; GX sPLA 2 −/− mice: 19.6±1%; p2 +/+ mice: 1300±26 um 2 GX sPLA 2 −/− mice: 2700±78 um 2 ; p2 +/+ mice: 46.3±4.9 mg/dl; GX sPLA 2 −/− mice: 33.8±2.9 mg/dl; p2 −/− and GX sPLA 2 +/+ mice. Compared to 3 month old GX sPLA 2 +/+ mice, the relative expression of IL-6 and F4/80 mRNAs in adipose tissue of age-matched GX sPLA 2 −/− mice was increased 9- and 4-fold, respectively, suggesting that the increased adiposity in GX sPLA 2 −/− mice was associated with an increase in the inflammatory profile of adipose tissue Conclusions: Our data points to a previously unrecognized role for Group X sPLA 2 in the development of obesity and associated adipose tissue inflammation.

Technology Focus Coupled, full-field, integrated, holistic, or asset: Call it what you will, this class of modeling is becoming increasingly commonplace. The ability to interrogate the response of a system, from the reservoir to fiscal meter, is quite potent and encourages integration in all senses of the word—technically, operationally, and organizationally. Such end-to-end models may reveal bottlenecks, constraints, and potential flow-assurance issues. While the benefits are manifest, two related issues are worthy of consideration: complexity and piloting. The complexity of any individual component (such as the reservoir model) refers to the engineering judgment required to ensure that it is fit for purpose. For example, should one use a simple model (computationally rapid but approximate) or should a more complex model (computationally slower but accurate) be adopted? The former is better suited for rapid scenario screening and sensitivity analysis, while the latter is better suited for detailed engineering, with a spectrum of models in between. Piloting is another consideration. The degree of technical insight required to competently steer any single component simulator is often quite high. Having several simulators under a single, seamless platform places an extra burden on the pilots involved because the added layer of software (the integration platform) may mask possible shortcomings in a model, thus rendering potentially incorrect results and even suboptimal capital decisions. These considerations notwithstanding, I am genuinely optimistic about the potential these full-field models will bring and the insights they can deliver. More articles are certain to appear detailing predictions vs. observations and how planning, operations, and economics benefited from such integrated studies. I respectfully submit that the story of fully coupled, full-field, integrated asset modeling has only just begun. JPT

This paper demonstrates the design, fabrication and testing of a diffractive element that converts the sinusoidal into linear scanning. The design approach is based on the beam propagation in inhomogeneous media.

Magnetic resonance imaging of patients with a metallic Intra-Orbital Foreign Body (IOFB) may be hazardous. Much controversy exists with regard to the optimum initial screening protocol to be undertaken which will ensure patients with metallic IOFBs do not enter the MR controlled area. Once a patient has been screened as ‘at risk', further variations in practice exist with regard to optimum imaging modality and radiographic technique to rule out the FB. This is due to a paucity of empirical research which is diverse in approach and conclusion. MR radiographers are developing their role and, as advanced practitioners, will find themselves increasingly involved in decision-making with regard to patient safety. Although it may feel a comfortable option to request a radiograph on all patients who pose a dilemma, MR radiographers need to be able to defend such a course of action through a thorough understanding of the financial and dose implications as discussed in the literature. This review will highlight some of the arguments both for and against screening patients for metallic IOFB and consider the radiographic screening options for ‘at risk' patients.

III-V based single photon avalanche diodes (SPADs), avalanche photodiodes (APDs) operated in Geiger-mode, are ideally suited for ultra-weak signal detection in the near infrared for photon counting and photon timing applications. Spaceborne SPADs would provide a rugged, compact alternative to photomultiplier tubes with lower operating voltage requirements, stronger near-IR response, and the possibility for array implementation. Results from a performance characterization of an in-house fabricated In0.53Ga0.47As/InP SPAD are presented. Sensitivity (NEP) and timing resolution (δt) were investigated as a function of bias from T = 135 K to 165 K; an NEP ≈ 5 x 1015W/Hz1/2 at T = 150 K and δt ≈ 230 ps at T = 165 K were measured for λ = 1.55 μm light.

Although frac-packing has been widely and successfully used in cased-hole completions, open-hole frac-packing is not so common. It is well known that the efficiency of cased-hole frac-packs can be limited by the perforations. It can therefore be expected that open-hole frac-packing would provide higher productivity by eliminating a major choke in the flow path. In this paper, we present an open-hole frac-pack case history involving a highly-deviated, challenging well in South East Asia and demonstrate the expected efficiency gains. The well was drilled in a field with a major water-flooding program. Due to extremely low reservoir pressure, low fracture-gradient and high kh formation (100,000 md-ft), very high losses were experienced. The presence of a high-pressure, reactive shale above the pay zone made it necessary to prematurely run a 7-in casing in order to isolate the problematic zone. However, due to the collapse of the reactive shale section, the casing was set above the target depth thereby exposing 70-ft of shale zone. Initial attempts to run the completion assembly failed due to the collapsed shales, resulting in a suspension of the well. After 4-months of water-flooding, partial re-pressurization of the reservoir was expected, and consequently a decision was made to complete the well with the open-hole frac-packing technique. In order to address complete coverage in a high kh zone completed as open-hole, the shunt technique was used. In order to prevent reactive shales from collapsing and mixing with the proppant during frac-packing, a cup-type packer was set inside the casing to divert flow through the shunt tubes and thus bypass the shale section. These procedures resulted in a complete pack of the entire, highly deviated open-hole interval, with an optimized tip screen-out as per design. The resulting PI of 13.4 bpd/psi compares favorably to cased-hole frac-packs (average PI of 2.5 with a best PI of 5.8), cased-hole gravel packs (average PI of 2.3 with a best PI of 4.7) and open-hole gravel packs (average PI of 10.0 and best PI of 19.6) in the same field, particularly considering the extremely high losses (thus the extent of damage) experienced during the drilling stage of this well. Detailed procedures are given along with operation execution and production results. An extension of this technique to long open-hole horizontal wells (injectors and producers), using modified tool configurations, is also discussed.

Technology Focus As the development of shale oil and gas becomes increasingly significant, so does the need for modeling tools for their accurate and timely forecasting. The basic question then arises: Are the simulation tools that we have suitable for the job? Can they explain, and ultimately forecast, the contribution to flow from natural or hydraulically induced fractures? Ultimately, we need to be confident that the results from such models are sufficiently reliable for decision-making purposes. As Alexandre Emerick stated in JPT (April 2014), “The goal is to generate models for production forecasting aiding the decision-making process involved in the development and management of petroleum reservoirs.” The ability to model this increasingly important asset class is one of the primary issues facing reservoir and simulation engineers today. Our existing arsenal of simulation tools is certainly time-tested for conventional assets, but can they deliver reliable forecasts for this emergent class? Recent literature is rich with relevant studies ranging from fundamental laboratory experiments to entirely empirical, data-driven, approaches for predictive reservoir management. These articles raise numerous questions, including the possible oversimplification of a complex problem, the very nature of the production mechanisms, and the role played by any pre-existing discrete fracture networks. Additional concerns relating to accuracy and reliability of the underlying data used to populate such models have also been raised. Keeping an open mind on this topic is, I feel, appropriate. One needs to balance the very real need for such predictive tools today with the recognition that future evidence may disrupt certain preconceptions. To this end, four articles have been selected that span a spectrum of ideas. One considers practical applications and solutions, while another covers the emerging technique of molecular simulation. Another eloquently probes various notions in our current state of understanding of shale assets and examines issues in interpreting the forecasts furnished by our simulation models. The fourth article demonstrates some creative thinking by representing a planar fracture by use of a proxy comprising a coupled flowing network model, a concept that may prove flexible and warrants further investigation. Conventional modeling tools used to predict flow in tight, fractured shales (e.g., dual-porosity models, local grid refinements, tartan grids) may, indeed, provide reliable forecasting. Analytic and data-driven approaches are also acceptable in some circumstances. However, as our knowledge in exploiting these assets deepens with new theory, laboratory experiments, and field and operational experience, we should be prepared to reconsider some of today’s axioms in the future.

Patient welfare requires routine follow-up procedures of implantable pacemakers. However, the assessment of atrial sensing and pacing functions in implantable pacemakers is often a challenge due to difficult identification of low amplitude P waves on surface electrocardiograms (ECGs). A previous body surface mapping study suggested that a novel P wave lead vector (P lead) had larger root mean square values than other standard leads. However, for pacemaker follow-up procedures, peak-to-peak amplitudes are more relevant than root mean square values. In this study, the peak-to-peak amplitudes of intrinsic and paced P waves recorded from surface ECG standard lead II and the P lead were compared. In addition, intrinsic and paced R waves were also compared. Data recorded from 15 patients undergoing electrophysiological studies indicated that peak-to-peak amplitudes of the P lead were significantly larger than standard lead II: 24% for intrinsic P waves, 30% for paced P waves, and 72% for intrinsic R waves. In addition, the P lead amplitude of paced R waves showed a nonsignificant increase of 24% compared with standard lead II. Therefore, the use of this new lead vector may improve the clinical ease-of-use and reduce the time required for follow-up procedures of implantable pacemakers for atrial sensing and pacing assessments.

This study examined the extent of influence which an extremely impoverished acoustic-linguistic system exerted on multitrial free recall of word lists, using 36 prelingual deaf and 36 normal-hearing S s of two age levels. In comparison with the hearing S s, the deaf S s′ recall performance was poor and their span of “echoic” memory tended to be short. Between the two groups, there was a considerable amount of common features in mnemonic organizations, as assessed by Tulving's subjective organization, Bousfield's clustering, and Johnson's hierarchical clustering schemes. The deaf S s were, however, less efficient and showed no developmental improvement in these measures. These results suggest that acoustic-linguistic mediation is also crucial for deaf S s′ free-recall learning of verbal materials.