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Summary An analysis is presented that quantifies the value-adding brought to a well by installing downhole flow control valves (FCVs) in a reservoir with uncertainties represented by multiple equiprobable realizations, two aquifer strengths, and three oil/water contacts (OWCs). The complexity of the model makes nonintuitive its response to FCV adjustment. From an openhole (OH) baseline net present value (NPV), it was possible to extract specific value-adding for the following, nonadjustable valves, the ability to adjust the valve, and how future information can add further value. The issue of measurement bin size is discussed, and the implication of making them too large, or too small, is described. Finally value erosion due to valve failure is also addressed. The solution presented used dynamic programming (DP), which was validated against a full enumeration of the problem using reservoir simulation. Approaches to proxies to traverse the (potentially large) decision space are also discussed.

Bowel dysfunction, in the form of constipation and/or incontinence, is one of the most prevalent and life-impacting co-morbidities associated with spinal cord injury (SCI) with no long- term treatment available. The extent to which SCI-induced changes in the colon (e.g. inflammation, fibrosis, and reduced enteric neuron density) cause progressive dysfunction is understudied. There remains a significant unmet need to develop strategies to prevent or reverse bowel dysfunction after SCI. This need remains, in part, due to the lack of a mouse model which recapitulates the human condition. We hypothesized that a T3 spinal transection in mice would trigger bowel dysfunction alongside early colonic inflammation and downstream remodeling of the colon musculature as seen in both humans and rats after SCI. Bowel dysfunction was defined as increased number of fecal pellets within the colon, smaller pellet size, and decreased water content in the stool. The number of fecal pellets within the colon increased significantly in animals receiving SCI compared to sham (laminectomy only) injuries by 4 days post injury (dpi) and persisted to 21dpi. Furthermore, fecal pellet size was significantly decreased in the SCI animals at 21dpi and trended toward decreased water content. Together, these functional measurements are indicative of chronic bowel dysfunction after T3 transection. We next molecularly interrogated whole colon tissue for inflammatory cytokine levels and found increased levels of IFN-γ at 4 dpi but not at 21dpi and found increased collagen deposition in the colonic musculature at both 4 and 21 dpi in the SCI versus sham animals. The acute spike in INF-γ and deposition of collagen after injury are consistent with our hypothesis that T3 transection causes acute inflammation followed by remodeling of the colon wall. Establishing this mouse model will enable further interrogation of cell-type specific responses and signaling pathways using transgenic models. T32 Fellowship in Physiology (GM118292) and T32 Fellowship Neurobiology of CNS Injury & Repair (5T32 NS077889) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

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.

The accumulation of pro-inflammatory macrophages in the inflamed vascular wall is a critical step in atherogenesis. The mechanism of macrophage retention within the site of inflammation is not understood yet. High adhesion that prevents macrophage migration is one of the potential mechanisms. We previously showed that integrin α D β 2 is upregulated on pro-inflammatory macrophages, promotes macrophage retention, and contributes to atherogenesis. However, we have not identified a key ligand for α D β 2 within the tissue, since α D β 2 does not interact with major ECM proteins, collagens, and laminins. We recently found that during acute inflammation, the oxidation of docosahexaenoic acid (DHA) leads to the generation of end product carboxyethylpyrrole (CEP), which forms an adduct with fibrinogen and albumin via ε-amino group of lysines. Moreover, we revealed that macrophages adhered to CEP-modified albumin in α D β 2 -dependent manner. Now we are testing a hypothesis that DHA oxidation is a universal mechanism during chronic inflammatory diseases that promotes the generation of CEP adducts with different ECM proteins and forms α D β 2 -mediated strong anchorage of macrophages, which is critical for macrophage retention during chronic inflammation. We detected CEP-modified proteins in digested atherosclerotic lesions by western blot. In vitro DHA oxidation leads to the formation of CEP adducts with collagen IV and laminin but not with collagen I. Using α D β 2 -transfected HEK293 cells, WT and α D -/- mouse macrophages, we revealed that CEP-modified proteins support stronger cell adhesion and spreading to compare with natural macrophage ligands. Using site-directed mutagenesis, we generated mutant α D I-domains and α D β 2 -transfected cells with single amino acid substitutions. Applying protein-protein binding and adhesion assays we detected one amino acid within integrin α D , K 246 , which is critical for α D β 2 binding to CEP-modified proteins. In summary, we propose a new mechanism of macrophage retention, which is based on inflammatory modifications of ECM with DHA end-product, CEP. The identification of a binding site for CEP-modified proteins within α D β 2 will help to develop a blocking reagent for the treatment of the inflammatory component of atherosclerosis.

To evaluate the clinical efficacy and patient satisfaction rates of low-intensity extracorporeal shockwave therapy LIESWT) in men with vasculogenic erectile dysfunction (ED) using Duolith SD1 machine.This prospective, randomized, double-blinded clinical trial included 60 men who were randomly assigned to LIESWT (n=30, active group) or placebo (n=30) over 6 weeks. Patient demographics, change in International Index of Erectile Function (IIEF)-5, Erection Hardness Score (EHS) and Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) scores, and an overall satisfaction score (on a 5-point scale), were recorded. All patients were reviewed at 1, 3, and 6 months after completion of therapy.There were 21 (70%) patients in the LIESWT group and 3 (10%) patients in the placebo group who had a 5-point or greater increase in IIEF-5 score (p=0.018). At 6-month study period, the mean IIEF-5 score was 18.8 (standard deviation [SD], 3.8) in the LIESWT group versus 14.8 (SD, 3.6) in the placebo group, difference in means between groups was 4.0 (95% confidence interval, 2.1-5.9; p0.001). The EHS scores were higher in the LIESWT group with a mean of greater than 1.2 across the 1, 3, and 6 months compared to the placebo group (p0.05). All patients completed the treatment study and there was no adverse event reported in terms of penile pain, bruising or deformity. There was a positive correlation between men who reported improvement in EF and treatment satisfaction level with LiESWT (p=0.008).LIESWT improves erectile function in the short-term especially in men with mild to moderate ED, and those without a cardiometabolic disease.

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

Animal cruelty cases can involve a variety of mistreatment to domestic animals. A common source of abuse is the use of heat sources, such as ovens, hot surfaces and microwaves. Analysis of damage to skin by a veterinarian is a key aspect of these investigations but additional information can be provided by observing the hair of the animal, including heat source type and exposure time. This study developed an objective grading system for the analysis of heat damage in hairs which can be used to quantify different damage characteristics including bubbling, discolouration, expansion of hair, fractures, changes to the medulla and scales and scale removal/melting. This grading scheme was applied to the investigation of dog (Canis familiaris) skin samples with full pelage and loose hairs exposed to microwaves and a heated environment in order to identify any distinguishing damage characteristics from the two different heated environments. Samples were exposed to a furnace for 1 min at different temperature ranges (50–350 °C with 50 °C intervals) and also a microwave at maximum power for different time periods (15, 30, 45, 60, 120, 180, 240 and 300 s). Hairs were extracted for examination using high powered light microscopy and scanning electron microscopy. Overall, it can be determined that the type of damage observed is influenced by the nature of heat applied and the context and substrate in which the hair is situated at the time of exposure. Using principal component analysis (PCA) it was concluded that as temperature increases in a furnace so does the severity of each of the damage characteristics observed. It can be noted that with furnace exposure, any one of the characteristics could be used to indicate the temperature to which it has been exposed. For furnace exposed samples there was no significant difference between loose or embedded hairs. PCA analysis determined that there are two independent forms of damage that occur when hairs are exposed to microwave radiation, these are: increased bubbling and discolouration in the root and increased bubbling and discolouration of the shaft and tip. Exposure time is correlated with both the root and shaft/tip observations. The results indicated some clear distinctions between heat source and exposure useful for the objective interpretation of such evidence. This standardised approach for the observation of heat damage characteristics in animal hair provides investigators with a tool to differentiate between methods of abuse, providing a greater understanding of the crime committed.

Narratives of unruly Black children in failing schools often normalize hopelessness at the expense of students. Newer, sometimes silenced voices, however, can produce counter-narratives that can lead to ecological solutions for assisting traumatized students. This is a case study of the transformation of a principal who asked, “What's wrong with these children?” to an advocate whose inquiry shifted to “What happened to these children, and what must we do to help them?” With trauma awareness and behavioral management training for her staff, improvements began. The local school board cut her successes short by changing the lock on her office door on the day before teachers returned for the Fall Semester and informed her that her services were no longer needed. What is the lesson for the consultant?

In this book, Barbara Ellison and Thomas B. W. Bailey lay out and explore the mystifying and evanescent musical territory of‘sonic phantoms’: auditory illusions within the musical material that convey a‘phantasmatic’ presence. Structured around a large body of compositional work developed by Ellison over the past decade, sonic phantoms are revealed and illustrated as they arise through a diverse array of musical sources, materials, techniques, and compositional tools: voices (real and synthetic), field recordings, instrument manipulation, object amplification, improvisation, and recording studio techniques. Somehow inherent in all music--and perhaps in all sound--sonic phantoms lurk and stalk with the promise of mystery and elevation. We just need to conjure them.

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.

After 9 years of contributing to JPT, it’s time to hang up my spurs. I’ve had the privilege of being exposed to a broad range of topics, technologies, and papers (good, bad, and indifferent). The technological advances I have observed, and the changes in our way of working, have been startling. I wanted to use this opportunity, however, to raise a couple of issues, namely the effect and utility of machine learning (ML) and the usage of point-and-click engineering software. Back in June 2018, I wrote an editorial outlining concerns I held regarding the promise of ML/artificial intelligence to resolve complex physics-based engineering problems. Nothing has changed my opinion since then. There is no doubt that ML has utility in advancing our understanding of certain problems, such as monitoring of large numbers of wells and preempting run-time problems. To claim that ML will provide an accurate forecast of, say, a new multi-phase network flow model, however, would be—let’s be diplomatic here—problematic. In my opinion, ML needs to be applied with surgical precision, not as a blunderbuss shot in the rough direction of a problem with hopes that a pellet will hit a target. It’s still too soon to draw conclusions on the broad utility of ML, but it is unlikely to prove to be the universal cure-all that some have promoted. The best way to summarize the what, where, and how, to apply ML is: It depends. Time will tell, and I remain hopeful but cautious. The other issue is a need to maintain an appreciation of the underlying physics of the problem being modeled. Continuously evolving software has enabled greater overview, visualization, and intricate analysis of ever-more-complex systems. This is a definite boon and provides a level of performance insight hitherto unheard of. Such software, however, still requires a pilot to operate it, and key inputs blunderbuss shot in the rough and physics may be masked, or even hidden, beneath a dazzling interface. Optimization of such systems is also nontrivial, yet this nontrivial task is now made almost pedestrian by a mere click of the mouse. It is so easy to accept software-generated solutions, even though they may turn out to be suboptimal (or even wrong) because of some errant input or a poorly defined parameter. I am a strong proponent of the amazing advances made in software, democratizing and seamlessly unifying other-wise specialist tools and disciplines. But no substitute exists for digging into the problem physics/mechanisms themselves and applying simple pen-and-paper (“back-of-the-envelope”) checks. So, the next time that gas bill arrives, I might suggest keeping the envelope it came in; one never knows when it may prove useful. Recommended additional reading at OnePetro: www.onepetro.org. SPE 203139 - Reduce Cost and Schedule by Developing an Optimum Well Surface Facility Program by Cathy Farina, DyCat Solutions, et al. SPE 206181 - Development of Methods for Top-Down Methane Emission Measurements of Oil and Gas Facilities in an Offshore Environment Using a Miniature Methane Spectrometer and Long-Endurance UAS by Brendan Smith, SeekOps, et al. OTC 30292 - Development of an Assessment Procedure To Predict Local Buckling Behavior Using Probabilistic Method With Finite-Element Techniques for Reeled Pipeline With Additional Features by Sheralia Ufairah Abdullah, McDermott International, et al.

A critical step in the development of chronic inflammatory diseases is the accumulation of proinflammatory macrophages in the extracellular matrix (ECM) of peripheral tissues. The adhesion receptor integrin α(D)β(2) promotes the development of atherosclerosis and diabetes by supporting macrophage retention in inflamed tissue. We recently found that the end product of docosahexaenoic acid (DHA) oxidation, 2-(ω-carboxyethyl)pyrrole (CEP), serves as a ligand for α(D)β(2). CEP adduct with ECM is generated during inflammation-mediated lipid peroxidation. The goal of this project was to identify a specific inhibitor for α(D)β(2)–CEP interaction that can prevent macrophage accumulation. Using a specially designed peptide library, Biacore-detected protein–protein interaction, and adhesion of integrin-transfected HEK 293 cells, we identified a sequence (called P5 peptide) that significantly and specifically inhibited α(D)–CEP binding. In the model of thioglycollate-induced peritoneal inflammation, the injection of cyclic P5 peptide reduced 3-fold the macrophage accumulation in WT mice but had no effect in α(D)-deficient mice. The tracking of adoptively transferred, fluorescently labeled WT and α(D)(−/−) monocytes in the model of peritoneal inflammation and in vitro two-dimensional and three-dimensional migration assays demonstrated that P5 peptide does not affect monocyte transendothelial migration or macrophage efflux from the peritoneal cavity but regulates macrophage migration through the ECM. Moreover, the injection of P5 peptide into WT mice on a high-fat diet prevents macrophage accumulation in adipose tissue in an α(D)β(2)-dependent manner. Taken together, these results demonstrate the importance of α(D)β(2)-mediated macrophage adhesion for the accumulation of infiltrating macrophages in the inflamed ECM and propose P5 peptide as a potential inhibitor of atherogenesis and diabetes.

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.

In the absence of mitigation measures, the ongoing effort to deepen the navigation channel in Georgia’s Port of Savannah would reduce dissolved oxygen levels in the Savannah River below what is needed to sustain ecological diversity. To prevent this scenario, a series of oxygen-injection cones will be installed in two locations to add 40,000 lb of dissolved oxygen per day to the waterway.

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.

Seismic modeling is commonly used in determining subsurface illumination of alternative seismic survey designs, in the calibration of seismic processing and imaging algorithms, and in the design of effective processing workflows. Seismic modeling also forms the mathematical kernel of impedance inversion and is routinely used to predict the amplitude-variation-with-offset response as a function of rock and fluid properties. However, the use of seismic modeling in seismic attribute studies is less common. We have evaluated four case studies in which 2D synthetic common shot gathers were computed (acoustic or elastic) and processed (including migration) to evaluate possible interpretation hypotheses. The modeling we used in our study shows that the lack of continuous coherence anomalies in a faulted Chicontepec Basin survey was due to overprinting by coherent interbed multiples. Attributes computed from the resulting processed model data revealed that subtle curvature anomalies in a Mississippi Lime survey were due to karst collapse rather than to velocity pushdown related to vertical gas migration. Impedance attributes computed from a Woodford Shale model favored the hypothesis of increased porosity correlated with the occurrence of subtle faults rather than amplitude dimming due to poor fault imaging. Finally, modeling of a fractured basement survey in the Texas Panhandle survey indicated that headwave suppression preserved the basement fracture response while increasing the signal-to-noise ratio. Seismic attribute study on seismic modeling results helped significantly in testing possible interpretation hypotheses in all of our case studies.

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 The original realm of this Technology Focus was reservoir simulation, but the scope has been expanded to include all simulation. This is, indeed, a broad sweep, and I fear that I may not be able to do full justice to technical domains in which I am not fully conversant. Nonetheless, muddling through, I have selected three papers with reasonably broad coverage. The one I particularly like describes an open-source 3D-printing micromodel tool kit. This highlights the need to validate simulation through experimental observation, and the work provides a practical means to do so. This will be my last editorial (it has been 6 years now), and I leave you with two main thoughts, one positive and one less so. My optimistic remark concerns the advances I have observed in the field of simulation of complex reservoirs, especially fracturing of tight reservoirs. While the topic remains challenging, the advances made have been quite significant over the past 5 years. Nonetheless, in my view, we still do not possess a full understanding of oil production in unconventional fractured reservoirs. Our ability to forecast such assets remains elusive, even with copious amounts of analytics, mountains of data, and an arsenal of machine-learning tools. We still cannot ascribe the level of confidence to such assets as we wish would be possible. More fundamental experimental investigation is necessary here, and, while we are gradually increasing our understanding, the journey has some way to go. My final comment concerns buttons. Specifically, I refer to these so-called big green “simulate” buttons: the ones that entice a user to blindly “press it, and for-get it” (with apologies to Ron Popeil). Well-crafted, user-experience-optimized, appealingly designed interfaces are now standard. Nothing new in that. Nonetheless, I cannot help but feel that, rather than assisting the engineer, such interfaces form a metaphorical barrier between the user and the simulation engine. I am of the generation that was quite happy navigating large keyword-driven ASCII files with the “vi” editor (remember that?). While these were awkward, slow, and often excruciatingly painful to operate, being forced to work directly with keywords and ASCII files yields one very significant advantage: an unavoidable and direct connection with the data. One had no choice but to become acquainted with all aspects of an important keyword and its input requirements. This ensured consistency of data input and facilitated a closer bond between user and simulator (greater transparency of what was going on under the hood). Being unashamedly old school, I feel that “optimized user-interface (UI) dashboards” often cast a misty veil over human/machine connectedness and sometimes may even impede the pathway to understanding of simulation behavior and the solution itself. My point here is this: Do not hesitate to dive into the files typically generated by these UIs and be unafraid to be old school, even if only for a few moments. The insight this affords is well worth the effort. Saying this, I am clearly showing my age, so it’s time for a fresh face to take over this editorial. I thank you for your patience over the past few years. Meanwhile, I feel an overwhelming urge to write another technical paper (that no one will read), written in TeX and coded in FORTRAN77, using my trusty “vi” editor—happiness awaits. Recommended additional reading at OnePetro: www.onepetro.org. SPE 191213 Application of Memory Formalism and Fractional Derivative in Reservoir Simulation by Mahamudul Hashan, Memorial University of Newfoundland, et al. SPE 193880 A Massively Parallel Algebraic Multiscale Solver for Reservoir Simulation on the GPU Architecture by A.M. Manea, Saudi Aramco, et al. SPE 193844 A Bayesian Sampling Framework With Seismic Priors for Data Assimilation and Uncertainty Quantification by Siavash Nejadi, University of Calgary, et al.

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.

Designing effective electronic information systems in real-world applications is a complex endeavor. Several factors, including the user's cognitive capabilities and limitations, the work domain and task constraints, and the content and form of the electronic medium, influence the interactive information-seeking process. This article presents an approach to model real-world information seeking in a corporate environment. Our approach uses self-reported user questionnaires, field studies of real-world professionals searching for information, and cognitive modeling techniques. This article presents modeling methodology, modeling results, and an overview of applying results to the design of human-centered interfaces used in a real-world electronic information system. © 1999 John Wiley & Sons, Inc.

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

Contrary to popular American myth, freedom of speech as a right of individuals in a participatory democracy is virtually nonexistent. As defined in Supreme Court case law, freedom of speech is conceived principally as the right of society to hear information. This essay argues that the collective right to hear, expressed as “the marketplace of ideas” is the portal through which corporate commercial/political speech entered and took over the marketplace of ideas. The symbiotic relationships between corporations, corporate media, and government enabled the takeover to be less than hostile. Short of social cataclysm, individual freedom of speech will probably play an increasingly diminished role in American public affairs.