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IntroductionThe use of Y-90 radioembolization techniques has become a standard tool for the treatment of liver cancer and metastatic diseases that result in liver lesions. As there are only two approved forms of radioembolization therapy, the procedures for use are also fairly standardized even though exact international and interdepartmental procedures can vary. What has been less published over the years are the nuanced differences in delivery techniques and handling of the two available Y90 radioembolization therapies. This paper seeks to examine various aspects of delivery techniques, product handling, and radiation exposure that differ between the available and approved products. Understanding these differences can assist with providing more efficient treatment, confirmation of accurate therapy, more informed handling of the products, and improved training of physicians and other hospital staff.MethodsTwo commercially available and approved radioembolization devices were compared to assess nuanced, but key differences between the available products regarding therapy delivery, handling of the products, and radiation exposure to patients and staff. This work is broken into two sections: (1) Therapy Delivery, (2) Radiation Safety. Therapy delivery characteristics were assessed by using an external radiation detector system with detectors placed inside of each delivery system facing the dose vial and on the output catheter lines to the patient. Additional detectors were placed near the liver of the patient and on top of the foot to measure extremities. Data were acquired continuously throughout therapy delivery to collect time activity curves (TACs) for the characterization of each therapy. These data were analyzed to assess if (a) real-time monitoring of radiation could be used to provide an accurate assessment of residual dose before the patient leaves the procedure room, and (b) can dose delivery characteristics be observed that enable improved training and quality control. Calculation of residual dose using the external detector TACs was performed by analyzing initial and final activity peaks to determine measured count rate differences. Radiation safety aspects were assessed by monitoring radiation exposure to staff handling each of the available therapy products. Nuclear medicine technologists and interventional radiology physician body and hand doses were measured for each delivered therapy using standard body and ring dosimeters. The TACs noted above collected for the liver and extremities were used to assess if any off-target or leached Y90 activity could be detected for each therapy. Blood was collected at times before, during, and after treatment and then counted on a gamma counter to assess differences in free Y90 circulating in the blood. Each patient in this study also received a post-treatment whole-body PET/CT at 2–4 h post-infusion to assess for any aggregate free Y90 deposition that may have resulted from circulating free Y90 in the subject following therapy.ResultsCalculations of residual dose in the vial following therapy using the real-time detection methods resulted in values that were not statistically different from the values calculated by nuclear medicine following the procedure (p>0.05). Real-time collection of dose delivery data enabled observation of key characteristics related to each delivery method. For SIR-spheres procedures, the cycle of pushing the dose and visualizing with fluoro can easily be seen with each push resulting in a smaller and smaller peak with intermittent fluoroscopy pulses. TheraSpheres infusions show a rapid bolus with nearly all of the measurable injected activity being infused in the first push of the dose. Staff radiation exposure assessments showed statistically significant differences between glass and resin spheres for hand doses of physicians and technologists (p > 0.05), but no statistical difference between body doses for both products (p>0.05). Assessments of free Y90 circulating during therapy showed that patients undergoing therapies with resin spheres had post-infusion blood levels that were 120% higher than pre-infusion levels while glass sphere therapy patients only saw a 7% rise in post-infusion blood levels. The coefficients of variation (COVs) across glass sphere measurements pre, during, and post, were only 0.008 while resin sphere measures saw much greater variability with a COV of 0.45. Both glass and resin therapies showed blood levels at 2–4 h post-injection to be similar to levels measured pre-injection. Neither therapy showed any signs of focal aggregation at 2–4 h post-infusion on whole-body PET/CT.ConclusionAlthough glass and resin radioembolization therapies are similar, they both have unique characteristics related to their administration and handling by staff. Understanding the nuances can assist in providing more efficient delivery, better staff education, and reducing radiation exposure to everyone involved with these therapies. The use of near real-time monitoring is feasible and can be used to obtain critical information about the delivery success of a therapy and can inform physicians on their techniques to optimize their practice as well as provide more consistent training to residents.

INTRODUCTION: Fibroblast growth factor receptor (FGFR)-4/FGF19 pathway dysregulation is implicated in hepatobiliary and other solid tumors. INCB062079, an oral, selective, FGFR4 inhibitor, inhibits growth in FGF19/FGFR4-driven liver cancer models. METHODS: This was a two-part, phase I study (NCT03144661) in previously treated patients with advanced solid tumors. The primary objective was to determine safety, tolerability, and maximum tolerated dose (MTD), while secondary objectives included pharmacokinetics, pharmacodynamics (plasma FGF19; bile acid salts/7α-hydroxy-4-cholesten-3-one [C4] levels), and preliminary efficacy. In Part 1, patients received INCB062079 starting at 10 mg once daily, with 3 + 3 dose escalation. Part 2 (dose expansion) was not conducted because of study termination. RESULTS: Twenty-three patients were treated (hepatobiliary, n = 11; ovarian, n = 9; other, n = 3). Among six patients receiving 15 mg twice daily, two patients had dose-limiting toxicities (DLTs; grade 3 diarrhea, grade 3 transaminitis). Both had high pretreatment C4 concentrations, prompting a protocol amendment requiring pretreatment C4 concentrations

BackgroundTargeting programmed cell death protein 1 (PD-1) and indoleamine 2,3-dioxygenase (IDO1) pathways is an appealing option for cancer treatment.MethodsThe open-label, phase 1/2 ECHO-203 study evaluated the safety, tolerability, and efficacy of the IDO1 inhibitor epacadostat in combination with durvalumab, a human anti-PD-L1 monoclonal antibody in adult patients with advanced solid tumors.ResultsThe most common treatment-related adverse events were fatigue (30.7%), nausea (21.0%), decreased appetite (13.1%), pruritus (12.5%), maculopapular rash (10.8%), and diarrhea (10.2%). Objective response rate (ORR) in the overall phase 2 population was 12.0%. Higher ORR was observed in immune checkpoint inhibitor (CPI)-naïve patients (16.1%) compared with patients who had received previous CPI (4.1%). Epacadostat pharmacodynamics were evaluated by comparing baseline kynurenine levels with those on therapy at various time points. Only the 300-mg epacadostat dose showed evidence of kynurenine modulation, albeit unsustained.ConclusionsEpacadostat plus durvalumab was generally well tolerated in patients with advanced solid tumors. ORR was low, and evaluation of kynurenine concentration from baseline to cycle 2,day 1, and cycle 5,day 1, suggested >300mg epacadostat twice daily is needed to ensure sufficient drug effect.Clinical trial informationA study of epacadostat (INCB024360) in combination with durvalumab (MEDI4736) in subjects with selected advanced solid tumors (ECHO-203) (NCT02318277).

Courtney Johnson,1 Jennifer Stephens,1 Christopher Walker,2 Joseph C Cappelleri,3 Ahmed Shelbaya4 1Pharmerit International, Real World Evidence and Data Analytics, Bethesda, MD, USA; 2Pfizer Ltd., Global Medical Affairs, Tadworth, Surrey, England; 3Pfizer Inc., Statistics, Groton, CT, USA; 4Pfizer Inc., Health Economics and Outcomes Research, New York, NY, USACorrespondence: Jennifer StephensPharmerit International, 4350 East West Highway, Suite 1100, Bethesda, MD, USATel +1 240-821-1290Email jstephens@pharmerit.comObjective: This study describes treatment patterns, healthcare resource utilization (HCRU), and costs associated with persistence, switching, and dosing of branded celecoxib in osteoarthritis (OA) patients.Methods: This retrospective claims database analysis used MarketScan® Commercial Claims and Encounters (MarketScan) data from 2009 to 2013. Included patients were adult (≥ 18 years), incident celecoxib users with ≥ 1 OA claim. The treatment switch analysis analyzed outcomes in patients persistent on celecoxib versus switched to a generic nonsteroidal anti-inflammatory drug (NSAID). The dosing analysis stratified patients as under-dose (< 200 mg per day) and standard dose (≥ 200 mg per day). HCRU, costs, and treatment duration were compared in persistent versus switched and standard dose versus under-dose patients using descriptive, multivariate logistic regression, and Kaplan–Meier analysis.Results: A total of 65,530 patients met the inclusion criteria. During follow-up, 83% discontinued celecoxib without switching, 10% were persistent, and 5% switched to a generic NSAID. Ninety percent received a standard dose of celecoxib. Switched (versus persistent) patients had significantly higher all-cause hospital admissions, length of stay, emergency room (ER) visits, and office visits per person year (PPY), all P < 0.001; and under-dosed (versus standard dose) patients had significantly higher hospital admissions (P< 0.001), length of stay (P< 0.001), and ER visits (P= 0.021) PPY. Persistent versus switched patients had lower mean total all-cause costs PPY ($20,378 vs $23,949, P< 0.001). Standard dose versus under-dose patients had lower mean total all-cause costs ($23,680 vs $26,955 PPY, P< 0.001), and not statistically significant higher mean total OA-related costs ($5698 vs $5524 PPY, P=0.441).Conclusion: Patients that switched from branded celecoxib to a generic NSAID or received an under-dose of branded celecoxib had higher average overall HCRU and costs. OA-related inpatient and outpatient cost savings may offset the higher drug cost of celecoxib for persistent patients.Keywords: generic, healthcare resource use, Celebrex, NSAIDS, switching, discontinuation

The role of immune responses to previously seen endemic coronavirus epitopes in severe acute respiratory coronavirus 2 (SARS-CoV-2) infection and disease progression has not yet been determined. Here, we show that a key characteristic of fatal outcomes with coronavirus disease 2019 (COVID-19) is that the immune response to the SARS-CoV-2 spike protein is enriched for antibodies directed against epitopes shared with endemic beta-coronaviruses and has a lower proportion of antibodies targeting the more protective variable regions of the spike. The magnitude of antibody responses to the SARS-CoV-2 full-length spike protein, its domains and subunits, and the SARS-CoV-2 nucleocapsid also correlated strongly with responses to the endemic beta-coronavirus spike proteins in individuals admitted to an intensive care unit (ICU) with fatal COVID-19 outcomes, but not in individuals with nonfatal outcomes. This correlation was found to be due to the antibody response directed at the S2 subunit of the SARS-CoV-2 spike protein, which has the highest degree of conservation between the beta-coronavirus spike proteins. Intriguingly, antibody responses to the less cross-reactive SARS-CoV-2 nucleocapsid were not significantly different in individuals who were admitted to an ICU with fatal and nonfatal outcomes, suggesting an antibody profile in individuals with fatal outcomes consistent with an "original antigenic sin" type response. ispartof: JCI INSIGHT vol:7 issue:13 ispartof: location:United States status: published

Introduction: Published guidelines recommend patients and carers are trained and meet competency in certain criteria of connecting and disconnecting procedures before discharge from hospital on hom...

Confronted with mixed evidence linking economic upgrading in global value chains to improved social outcomes, proponents have called for a new emphasis on “social upgrading” to promote better employment, gender equality, and poverty reduction. Originally focused on a central role for states, unions, and social movements, the discourse on social upgrading has shifted, emphasizing the benefits of corporate social responsibility and global markets. Drawing on political economic, critical theory, and psychoanalytic paradigms, we explore the politics of this shift and argue that social upgrading is gradually being deployed as a neoliberal market fantasy, designed not to challenge the limits of market integration, but to obscure and deny them. The strength of the social upgrading discourse emerges less from its pretense toward objective, data-driven analysis, than its effectiveness as an ideological fantasy in meeting the contradictory, non-rational desires of experts and non-experts.

In evaporite basins, salt deformation including inflation, diapirism, and salt canopy emplacement is inherently non-coaxial and ductile and thus it presents challenges for two-dimensional kinematic restorations that rely on line-length and area-balancing assumptions. Also, because salt flow and the resulting deformation of adjacent cover units can be driven by temporally and spatially transient salt pressure gradients, kinematic restorations are generally unable to predict the magnitude and distribution of subseismic deformation that results from a particular structural scenario. Here, we use a case study from the Atwater fold belt, Gulf of Mexico, to test a new workflow that involves comparison of kinematic restoration models with forward numerical (finite-element) models of structural evolution to examine the physical validity of solutions derived from the kinematic restorations and to determine the nature and spatial distribution of the resultant subseismic deformation. In the Atwater fold belt, which represents the downdip portion of a linked updip (landward) extensional-downdip (seaward) contractional system, our kinematic restorations indicated that major anticlines likely result from early short wavelength folding followed by (1) inflation of the autochthonous salt to drive failure of the overburden, (2) collapse of the updip limb of the major salt-cored anticline as the salt evacuates updip, and (3) rapid emplacement of the allochthonous salt canopy. In margin scale finite element models of the same system, progradation of the sedimentary wedge above the weak salt substrate leads to basinward migration of the salt and produces inflation of the major downdip salt-cored folds, as predicted by the kinematic model. However, in relatively strong overburden materials (equivalent friction angle = 32°), such salt flow only sustains inflation of the anticlines and is unable to reproduce the interpreted collapse of the anticlinal backlimb or emplacement of the salt canopy. Alternate model runs that include a significant reduction in material strength (equivalent friction angle = 18°) allow salt in the anticlinal crest to drive both reactive and active diapirism and ultimately lead to rapid emplacement of allochthonous canopies. In all of these models, diapirism drives substantial seismically-resolvable and subseismic deformation of wall rocks. Additionally, these models clearly show that the stress field, and particularly the K value (horizontal-vertical stress ratio) of the sediments adjacent to salt structures used for estimating stress magnitudes for drilling predictions, is fundamentally dependent on what point along the evolutionary path from autochthonous salt, to diapir, to salt sheet, that each structure resides. These results highlight the need to test complex kinematic restorations with physics-based techniques. Additionally, they demonstrate that integrating kinematic restorations with these finite element solutions can substantially increase our ability to predict both subseismic reservoir damage in sediments adjacent to salt structures and the K values used for forecasting drilling conditions, particularly in young basins filled with poorly consolidated sediments.

Constructed floating wetlands (CFWs) promote the growth of plants in buoyant structures where nutrients can be assimilated into biomass, and thus offer an alternative treatment that is potentially more economically viable than conventional constructed wetlands (CWs). This study examined the hydroponic growth of native Australian plants including Baumea rubiginosa (BR) and Phragmites australis (PA) in a synthetic water mix representing both stormwater and municipal waste water, and their total nitrogen (TN) and total phosphorus (TP) uptake rate over a 35-week period. With increases in the nutrient levels in synthetic waters, the overall dry weight of both roots and shoots, and the accumulated TN and TP values removed from the system, all increased. For both storm and waste waters, BR was found to have a higher overall shoot weight compared to that for the PA. In waters with relatively high nutrient levels, BR was found to have a lower overall root weight compared to that for the PA. The %TN accumulated in all plant root tissue was found to be greater than the shoot tissue and consequently the TN removal efficacy by PA (species with a relatively high growth rate of roots) was high in comparison to that by BR (species with a relatively high growth rate of shoots). The TP removal efficacy by BR was higher than that of PA. These results show that CFWs with native plant species could be used to reduce the nutrients levels in both stormwater and wastewater under a Mediterranean climate condition. Refereed/Peer-reviewed

Viktor V Chirikov,1 Chris Walker,2 Jennifer M Stephens,1 Patricia Schepman,3 Richard Chambers,4 Mahmoud Bakir,5 Gregory W Poorman,1 Seema Haider,6 Mohammed Farghaly7 1OPEN Health, Bethesda, MD, USA; 2Global Medical Affairs, Viatris, Tadworth, UK; 3Global Health Economics and Outcomes Research, Pfizer Inc, New York, NY, USA; 4Biostatistics, Pfizer Inc, Collegeville, PA, USA; 5Upjohn Export B.V., Jeddah, Saudi Arabia; 6Pfizer Inc., Groton, CT, USA; 7Dubai Medical College, Dubai, United Arab EmiratesCorrespondence: Jennifer M StephensOPEN Health, Bethesda, MD, USATel +1 703 625 5943Email jstephens@pharmerit.comObjective: Data on osteoarthritis patients from the PRECISION trial were used to evaluate the cost-effectiveness of celecoxib (100 mg twice daily) versus ibuprofen (600– 800 mg three times daily) and naproxen (375– 500 mg twice daily). The perspective was that of the United Arab Emirates (UAE) healthcare system.Methods: Discrete-state Markov model with monthly cycles, 30-month horizon, and 3% discount rate was constructed to assess incremental costs per quality adjusted life year (QALYs) gained from reduced incidence of three safety domains examined in PRECISION: renal, serious gastrointestinal (GI), and major adverse cardiovascular events (MACE). Costs for managing these toxicities were derived from Dubai Administrative Billing Claims (2018). Median monthly drug costs were derived from UAE Ministry of Health and Prevention’s published prices ($26.98 celecoxib; $20.25 ibuprofen; $20.50 naproxen). Health utility and excess mortality associated with toxicities were sourced from the literature. The willingness-to-pay thresholds used were 1 and 3 GDP per capita ($40,000–$120,000).Results: The total average cost per patient was $812.88 for celecoxib, $775.26 for ibuprofen, and $731.17 for naproxen while cost components attributed to toxicities were lowest with celecoxib ($360.26, $438.31, and $388.60, respectively). Patients on celecoxib had more QALYs (1.339), compared with ibuprofen (1.335) and naproxen (1.337), resulting in an incremental cost-effectiveness ratio of $11,502/QALY gained for celecoxib versus ibuprofen and $39,779 for celecoxib versus naproxen. Probabilistic sensitivity analyses demonstrated celecoxib to be 81% cost-effective versus ibuprofen and 50% versus naproxen at $40,000/QALY. The most influential model parameters were MACE relative safety and drug costs.Conclusion: From UAE third payer perspective, celecoxib is a long-term cost-effective treatment for osteoarthritis patients when compared with ibuprofen, and equally likely as naproxen to be cost-effective. With the expected increasing burden of chronic diseases in the Gulf region, study findings can inform decisions regarding the cost-effective pain management of osteoarthritis in UAE.Clinicaltrials.gov Registration Number: NCT00346216.Keywords: Markov, NSAIDs, comparative effectiveness, safety, Gulf region, AfME, MENA

Globally, osteoarthritis (OA) is the most prevalent arthritic condition in those aged over 60 years. OA has a high impact on patient disability and is associated with a significant economic burden. Pain is the most common first sign of disease and the leading cause of disability. Data demonstrating the increasing global prevalence of OA, together with a greater understanding of the burden of the disease, have led to a reassessment of the seriousness of OA and calls for the designation of OA as a serious disease in line with the diseases impact on comorbidity, disability, and mortality. While OA was traditionally seen as a prototypical 'wear and tear' disease, it is now more accurately thought of as a disease of the whole joint involving cartilage together with subchondral bone and synovium. As more has become known of the pathophysiology of OA, it has become increasingly common for it to be described using a number of overlapping phenotypes. Patients with OA will likely experience multiple phenotypes during their disease. This review focuses on what we feel are three key phenotypes: post-trauma, metabolic, and aging. A greater understanding of OA phenotypes, particularly at the early stages of disease, may be necessary to improve treatment outcomes. In the future, non-pharmacological and pharmacological treatments could be tailored to patients based on the key features of their phenotype and disease pathway.

Despite significant treatment advances, diabetes outcomes remain suboptimal and health care costs continue to rise. There are limited data on the feasibility and financial implications of integrating a diabetes-specific care team in the primary care setting (ie, where the majority of diabetes is treated). This pragmatic quality improvement project investigated whether a cardiometabolic care team intervention (CMC-TI) could achieve greater improvements in clinical, behavioral, and cost outcomes compared to usual diabetes care in a large primary care group in Southern California. Over 12 months, n = 236 CMC-TI and n = 239 usual care patients with type 1 or 2 diabetes were identified using the electronic medical record. In the CMC-TI group, a registered nurse (RN)/certified diabetes educator care manager, medical assistant health coach, and RN depression care manager utilized electronic medical record-based risk stratification reports, standardized decision-support tools, live and remote tailored treatments, and coaching to manage care. Results indicated that the CMC-TI group achieved greater improvements in glycemic and lipid control, diabetes self-management behaviors, and emotional distress over 1 year compared with the usual care group (all P

Para muchos el analisis de los Objetivos de Desarrollo del Milenio de las Naciones Unidas (MDG en ingles) deja unas imagenes de comunidades pobres y marginalizadas en el sur global que reciben apoyo financiero, prestamos, y apoyo de varias ONG del norte global. Pero, ?puede un pais del sur global, con recursos muy limitados, alcanza tanto los MDG como los Objetivos de Desarrollo Sostenible (SDG en ingles), y hacerlo sin el apoyo, apoyo financiero del norte global y la industria de desarrollo? El caso de Cuba, y su estrategia de desarrollo sostenible, podria ofrecernos algunas pautas sobre la forma de superar estos retos. En particular este articulo analiza los exitos de Cuba al cumplir con los objetivos, tanto de MDG como de SDG, en cuestiones de salud publica, educacion, igualdad de genero y medio ambiente. For many, discussion of the UN's development goals inspires images of poor and marginalised communities in the global south receiving aid, loans, and NGO support from the global north. Can a country from the global south with limited resources reach the UN's Millennium Development Goals (MDGs) as well as the Sustainable Development Goals (SDGs) and do so without the support, aid or influence of the global north and the development industry? The case of Cuba and its sustainable development approach may offer some evidence for overcoming these challenges. In particular, this article will examine Cuba's successes in meeting MDG and SDG targets in healthcare, education, gender equality and the environment.

Molecular simulations such as molecular dynamics (MD) and Monte Carlo (MC) simulations are powerful tools allowing the prediction of experimental observables in the study of systems such as proteins, membranes, and polymeric materials. The quality of predictions based on molecular simulations depend on the validity of the underlying physical assumptions. physical_validation allows users of molecular simulation programs to perform simple yet powerful tests of physical validity on their systems and setups. It can also be used by molecular simulation package developers to run representative test systems during development, increasing code correctness. The theoretical foundation of the physical validation tests were established by MerzShirts (2018), in which the physical_validation package was first mentioned.

During appraisal of an undeveloped segment of a producing offshore oilfield, three well penetrations revealed unexpected complexity and compartmentalization. Business decisions on whether and how to develop this segment depended on understanding the possible interpretations of the subsurface. This was achieved using the following steps that incorporated a novel practical application of Bayesian logic. 1. Scenarios were identified to span the full range of possible subsurface interpretations. This was achieved through a facilitated cross-disciplinary exercise including external participants. The exercise generated 12 widely differing subsurface scenarios, which could be grouped into 4 types of mechanisms: slumping, structural, depositional, and diagenetic. 2. Prior probabilities were assigned to each scenario. These probabilities were elicited from the same subsurface team and external experts who performed step 1, using their diverse knowledge and experience. 3. The probabilities of each scenario were updated by evaluating them sequentially with 21 individual pieces of evidence, progressively down-weighting belief in scenarios that were inconsistent with the evidence. For each piece of evidence, the likelihood (chance that the scenario could produce the evidence) was estimated qualitatively by the same team using a “traffic-light” high-medium-low assessment. Offline, these were converted to numerical likelihood values. Posterior probabilities were derived by multiplying the priors by the likelihoods and renormalizing to sum to unity across all of the scenarios. 4. The most probable scenarios were selected for quantitative reservoir modeling, to evaluate the potential outcomes of business decisions, given each scenario. Of the 12 scenarios identified in step 1, most were strongly down-weighted by the sequential revisions against evidence in step 3; after this, only scenarios in the “slumping” group retained significant posterior probabilities. The data showed minimal sensitivity to the initial assumption of prior probability in step 2. This process had several benefits. First, it encouraged the subsurface team to imagine a full range of scenarios that were likely to bracket the actual subsurface “truth,” something that is critical for subsequent decision-making. Second, it allowed belief in the probability of each scenario to be updated systematically in a way that was strongly conditioned to the evidence, so that the choice of scenarios to take through to reservoir modeling was more objective and evidence-based. Third, it allowed an assessment of the usefulness of individual pieces of evidence, which could be used to guide value-of-information assessments for subsequent data acquisition. Finally, the process enabled rigorous Bayesian revision methods to be applied in a simple practical way that engaged the subsurface team without exposing them to the underlying mathematics. During field appraisal and development, when the subsurface is revealed gradually as more data are acquired and studied, the process outlined here provides a practical way of generating and modifying belief in a range of subsurface scenarios while minimizing exposure to potential biases and logical fallacies that could affect subsequent decision quality. It also helps to decide which scenarios are sufficiently probable that they need to be represented by detailed reservoir models.

Since 1960, the Cuban government has been providing health care internationalism programmes throughout the globe. Despite the now overwhelming international recognition for Cuba’s medical efforts, protests against Cuban medical personnel working abroad are not uncommon. This article analyzes comparable patterns of protest in Brazil, Bolivia, and Haiti, where the protests have been driven primarily by ideological and class biases, as well as the Venezuelan case, where Cuban initiatives have been more politicized than elsewhere.

Jaspers and Popper have nothing in common beyond the legacy of Immanuel Kant’s philosophy. Popper dismisses Jaspers ‘existentialism’ as nihilistic and historicist; Jaspers never cites Popper. Jaspers describes Kant as ‘the philosopher for me’; Popper is an unorthodox Kantian whose critical rationalism put the finishing touch to Kant. For Kant, knowledge is not a simple copy of reality, but begins with reason’s questioning. Jaspers and Popper too insist that theory has priority over observation. For Jaspers, ‘there is already theory in every fact’; for Popper, ‘every statement has the character of a theory’. Science begins with metaphysical Ideas which become scientific when tested in experience. They differ in Popper’s rejection of induction in favour of falsification, while Jaspers tacitly accepts induction.

Faults play an important role in the trapping and development of many hydrocarbon accumulations around the world. Faults may form the ultimate updip sealing component responsible for containing hydrocarbons in a trap or they may provide a pathway for fluids to fill or leak out of a trap. During production, faults may compartmentalize a field into multiple different segments or they may connecting separate reservoir levels together. Many compilations of fault parameters have shown that the ratio between the displacement and length of a fault tends to fall in a range between 1:10 and 1:100. For soft, sedimentary rocks with relatively simple deformational histories that make up the majority of economical reservoirs for the conventional hydrocarbon industry, this ratio can be even narrower, between 1:20 and 1:50. This information can be used by the structural geologist to help map and assess the validity of a fault framework in an area. Individual faults in a distribution should follow this predictive model, and, if they fall outside the range commonly observed in nature, an alternate explanation should be sought. These explanations may call into question the interpretation of the fault, the horizon, and the fault linkages, as well as the applicability of the standard model to the specific mapped faults. In this chapter we will use to length-to-throw ratios measured on the fault framework to assess the validity of the structural interpretation, and propose alternatives interpretations that may be more in line with what is predicted from the observed global dataset.

Objective To compare the efficacy and safety of two different doses of celecoxib and diclofenac in the treatment of Norwegian patients with ankylosing spondylitis. Methods In this 12-week, double-blind, non-inferiority trial patients were randomized to 200 mg once daily (qd) celecoxib, 400 mg qd celecoxib, or 50 mg three times daily (tid) diclofenac. The primary objective compared patients’ assessments of Global Pain Intensity, measured on a visual analogue scale. Results A total of 330 patients were randomized (200 mg celecoxib, n = 107; 400 mg celecoxib, n = 108; diclofenac, n = 115). Least squares mean changes in Global Pain Intensity at 12 weeks were −25.8 mm, −30.6 mm and −28.2 mm, respectively. Both celecoxib treatment groups were non-inferior to diclofenac. More patients in the 400 mg celecoxib group met the Assessments in Ankylosing Spondylitis 20 responder criteria at Week 12 (60.2%) than in the celecoxib 200 mg (51.4%) and the diclofenac 50 mg (57.4%) groups. Adverse events were mild-to-moderate in severity, with dyspepsia and diarrhoea the most commonly reported. Conclusions Celecoxib and diclofenac both provided pain reduction, in addition to improvements in disease activity and functional capacity, in patients with ankylosing spondylitis.

Lesbian, gay, bisexual, or transgender (LGBT) older adults are often unaware or fearful of aging services that contribute to greater vulnerability, isolation, and risk when services are needed. In addition, they may perceive or experience bias in health care encounters. Providers may not recognize their own biases or their impact on such encounters. In response, a group of LGBT community activists, aging professionals, researchers, and a theatre ensemble developed an interactive theatre experience, described herein, that portrays challenges faced by LGBT older adults needing services. Goals included raising awareness among LGBT older adults and providers about issues such as the limited legal rights of partners, limited family support, and fear of being mistreated as a result of homophobia. Evaluations and feedback reflected the potential of interactive theatre to engage people in sensitive discussions that can lead to increased awareness, reduced bias, practice change, and ultimately improved care for LGBT older adults.

Purpose The aim of this work was to determine, by measurement and independent monitor unit (MU) check, the optimum method for determining collimator scatter for an Elekta Synergy linac with an Agility multileaf collimator (MLC) within Radcalc, a commercial MU calculation software package. Methods The collimator scatter factors were measured for 13 field shapes defined by an Elekta Agility MLC on a Synergy linac with 6 MV photons. The value of the collimator scatter associated with each field was also calculated according to the equation S c = S c mlc + S c corr ( S c open − S c mlc ) with S c corr varied between 0 and 1, where S c open is the value of collimator scatter calculated from the rectangular collimator-defined field and S c m l c the value using only the MLC-defined field shape by applying sector integration. From this the optimum value of the correction was determined as that which gives the minimum difference between measured and calculated Sc. Single (simple fluence modulation) and dual-arc (complex fluence modulation) treatment plans were generated on the Monaco system for prostate volumetric modulated-arc therapy (VMAT) delivery. The planned MUs were verified by absolute dose measurement in phantom and by an independent MU calculation. The MU calculations were repeated with values of S c corr between 0 and 1. The values of the correction yielding the minimum MU difference between treatment planning system (TPS) and check MU were established. Results The empirically derived value of S c corr giving the best fit to the measured collimator scatter factors was 0.49. This figure however was not found to be optimal for either the single- or dual-arc prostate VMAT plans, which required 0.80 and 0.34, respectively, to minimize the differences between the TPS and independent-check MU. Point dose measurement of the VMAT plans demonstrated that the TPS MUs were appropriate for the delivered dose. Conclusions Although the value of S c corr may be obtained by direct comparison of calculation with measurement, the efficacy of the value determined for VMAT-MU calculations are very much dependent on the complexity of the MLC delivery.

Summary METIS is a new disruptive onshore acquisition method developed by Total and its partners Wireless Seismic Incorporated and Geokinetics. It is designed to revolutionize the foothills seismic acquisition survey by combining a unique wireless real time seismic receiver and an innovative deployment by Unmanned Aerial Vehicles. A first pilot in one of the most challenging foothills environment on the planet was performed end of 2017 and presented in this abstract.

Ahmed Shelbaya,1,2 Caitlyn T Solem,3 Chris Walker,4 Yin Wan,3 Courtney Johnson,3 Joseph C Cappelleri1 1Pfizer Inc., New York, NY, 2Columbia School of Public Health, New York, NY, 3Pharmerit International, Bethesda, MD, USA; 4Pfizer Ltd., Tadworth, Surrey, UK Objective: This study aimed to evaluate the characteristics associated with early versus late initiation of celecoxib treatment after osteoarthritis (OA) diagnosis and whether economic and safety outcomes differ between patients with early versus late initiation of celecoxib.Methods: Adults (≥18 years) with a confirmed OA diagnosis (International Classification of Diseases, 9th Edition, Clinical Modifications code: 715.XX), ≥12 months of continuous pre- and post-index enrollment, and ≥1 post-index claim for celecoxib were included from the MarketScan® Commercial Claims and Encounter Database (2009–2013). Index date was defined as initial OA diagnosis. Patients were categorized as initiating celecoxib early (within 6 months of index date) or late (≥6 months after index date). Logistic regressions were used to assess characteristics associated with early versus late celecoxib initiation. Key outcomes included health care resource utilization (HCRU) and costs post-index, and adverse event incidence post-celecoxib initiation. Unadjusted and adjusted comparisons (using generalized linear models with a gamma distribution for costs and Poisson distribution for event and resource utilization) were made between early and late celecoxib initiators.Results: Of the 62,434 OA patients identified, 27,402 were early and 35,032 were late initiators. Post-index hospital admissions and length of stay did not differ statistically between early versus late initiators after controlling for pre-index event rates and covariates, but early patients had significantly fewer outpatient (incidence rate ratio [IRR]: 0.96; 95% confidence interval [CI]: 0.95, 0.97) and emergency room visits (IRR: 0.89; 95% CI: 0.84, 0.95). After adjustment for key covariates, early initiators (versus late initiators) had lower all-cause (US$12,909 versus US$13,781, P