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Background: There is increased recognition that cancers of the upper GI tract comprise distinct epidemiological and molecular entities. Erlotinib has shown activity in patients with adenocarcinoma of the oesophagus/gastro-oesophageal junction (GEJ), but not in distal gastric cancer. mFOLFOX6 is one of several active regimens used to treat adenocarcinoma of the Eso/GEJ. This study evaluates the efficacy and safety of mFOLFOX6 and erlotinib in patients with metastatic or advanced Eso/GEJ cancers. Methods: Patients with previously untreated advanced or metastatic Eso/GEJ adenocarcinoma are treated with oxaliplatin 85 mg m –2 , 5-FU 400 mg m –2 , LV 400 mg m –2 on day 1, 5-FU 2400 mg m –2 over 48 h and erlotinib 150 mg PO daily. Treatment was repeated every 14 days. The primary objective was response rate (RR), secondary objectives include toxicity, progression-free survival (PFS), overall survival (OS) and to correlate clinical outcome with expression patterns and molecular alterations in the epidermal growth factor receptor-dependent pathways. Results: A total of 33 patients were treated and evaluable: there were two complete responses, 15 partial responses for an objective RR of 51.5% (95% CI, 34.5–68.6%). Median PFS was 5.5 months (95% CI, 3.1–7.5 months) and median OS was 11.0 months (95% CI, 8.0–17.4 months). The most common grade 3–4 toxicities were: diarrhoea (24%), nausea/vomiting (11%), skin rash (8%) and peripheral neuropathy (8%). The frequency of alterations was KRAS mutations (8%), EGFR mutations (0%) and HER2 amplification (19%). Conclusion: In patients with Eso/GEJ adenocarcinoma, mFOLFOX6 and erlotinib is active, has an acceptable toxicity profile and FOLFOX±erlotinib could be considered for further development.

Background:The efficacy and safety of upadacitinib (UPA), a selective Janus kinase inhibitor, has been evaluated in the SELECT rheumatoid arthritis (RA) clinical program,1–6 but its real-world effectiveness remains to be investigated. The UPwArds study will assess the association of C-reactive protein (CRP) level with remission and other efficacy outcomes in patients with RA treated with UPA in German real-world practice.Objectives:To describe the baseline characteristics of patients enrolled in the UPwArds study.Methods:The prospective, open-label, multicenter, non-interventional, post-marketing UPwArds study included adult patients with moderate-to-severe RA (swollen joint count [SJC28] ≥3 and inadequate response or intolerance to ≥1 disease-modifying antirheumatic drug [DMARD]). Patients were treated with UPA 15 mg once daily, as monotherapy or in combination with methotrexate (MTX; 50:50 mono:combo enrollment planned), according to the German label. Variables assessed included medical history (disease duration, previous RA therapy, and vaccination status), CRP level, and disease activity (disease activity score [DAS28(CRP)], tender joint count [TJC28], and SJC28). There was no recruitment restriction regarding CRP level. This descriptive interim analysis reports patient baseline characteristics after enrollment was complete. All data were analyzed as observed, with no imputation of missing data.Results:533 patients (UPA monotherapy: 257 [48%]; UPA plus MTX: 276 [52%]) were included. Mean patient age was 58 years; mean disease duration was 9 years (Table 1). Despite having active RA, almost half the population (44%; n=237) did not have elevated CRP at the start of UPA treatment. Mean DAS28(CRP) was 4.6; mean TJC28 and SJC28 were 7.7 and 5.6, respectively. Overall, 39% of patients had not been treated with any biologic (b) DMARD or targeted synthetic (ts) DMARD before enrollment; 25% and 36% had previously been treated with 1 or ≥2 bDMARDs or tsDMARDs, respectively (Figure 1). 8.7% of patients had previously received a herpes zoster vaccination (8.1% Shingrix; 0.6% Zostavax).Conclusion:In German clinical practice, the population of patients with RA in the UPwArds study was predominantly treatment-refractory. Half of these patients had no elevated CRP despite active disease; future analyses will assess the impact of CRP on efficacy outcomes.References:[1]Smolen JS, et al. Lancet 2019;393:2303–11;[2]Burmester GR, et al. Lancet 2018;391:2503–12;[3]Genovese MC, et al. Lancet 2018;391:2513–24;[4]van Vollenhoven R, et al. Arthritis Rheumatol 2020;72:1607–20;[5]Fleischmann R, et al. Arthritis Rheumatol 2019;71:1788–800;[6]Rubbert-Roth A, et al. N Engl J Med 2020;383:1511–21.Table 1.Baseline characteristicsAge, yearsUPAUPA + MTXTotal57.7 (13.2) n=25758.1 (11.4) n=27657.9 (12.3) n=533Disease duration, years9.4 (8.3)8.5 (7.7)9.0 (8.0)n=253n=272n=525CRP, mg/dL1.3 (1.9)1.1 (1.7)1.2 (1.8)n=257n=276n=533CRP >ULN, n (%)137 (53.3)159 (57.6)296 (55.5)n=257n=276n=533TJC287.4 (6.0)7.9 (6.4)7.7 (6.2)n=257n=276n=533SJC285.5 (3.7)5.6 (4.1)5.6 (3.9)n=257n=276n=533Patient’s Global Assessment6.2 (1.9)6.3 (1.8)6.3 (1.8)n=257n=276n=533Physician’s Global Assessment5.8 (1.5)5.9 (1.6)5.9 (1.6)n=257n=276n=533DAS28(CRP)4.6 (1.0)4.6 (1.0)4.6 (1.0)n=257n=276n=533DAS28(ESR)4.8 (1.1)4.9 (1.2)4.9 (1.1)n=224n=239n=463CDAI24.9 (10.2)25.7 (10.8)25.4 (10.5)n=257n=276n=533SDAI26.2 (10.5)26.9 (11.3)26.6 (10.9)n=257n=276n=533RAID5.7 (2.0)5.7 (2.0)5.7 (2.0)n=255n=275n=530Pain (RAID-1)6.2 (2.2)6.1 (2.3)6.2 (2.2)n=255n=275n=530SF-12 Physical Component Summary32.6 (8.5)33.9 (8.6)33.3 (8.6)n=245n=262n=507SF-12 Mental Component Summary42.4 (11.6)42.6 (11.3)42.5 (11.5)n=245n=262n=507HAQ-DI1.3 (0.7)1.3 (0.6)1.3 (0.6)n=250n=270n=520PHQ-98.9 (5.3)8.6 (5.3)8.7 (5.3)n=252n=272n=524Erosions, n (%)87 (33.9)95 (34.4)182 (34.1)n=257n=276n=533Data are mean (SD), n unless otherwise statedAcknowledgements:AbbVie funded this study; contributed to its design; participated in data collection, analysis, and interpretation of the data; and in the writing, review, and approval of the abstract. AbbVie and the authors thank all study investigators for their contributions and the patients who participated in this study. No honoraria or payments were made for authorship. Medical writing support was provided by Grant Thomas Kirkpatrick, MSc, of 2 the Nth (Cheshire, UK), and was funded by AbbVie.Disclosure of Interests:Torsten Witte Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Chugai, Gilead, Janssen, Lilly, MSD, Mylan, Novartis, Pfizer, Roche, and UCB., Uta Kiltz Consultant of: AbbVie, Biocad, Eli Lilly and Company, Grünenthal, Hexal, Janssen, MSD, Novartis, Pfizer, Roche, and UCB, Grant/research support from: AbbVie, Amgen, Biogen, Fresenius, GSK, Hexal, Novartis, and Pfizer, Florian Haas Consultant of: AbbVie, Celgene, Novartis, and Pfizer, Grant/research support from: AbbVie, BMS, Celgene, Chugai, MSD, Novartis, Pfizer, Roche, and Sanofi Genzyme, Elke Riechers Consultant of: AbbVie, Chugai, Novartis, and UCB, Grant/research support from: AbbVie, Chugai, Lilly, Janssen, Novartis, Pfizer, Roche, and UCB, Ulrich Prothmann Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Chugai, Glaxo Smith Kline, Novartis, Pfizer, Roche, Sanofi, SOBI, and UCB, Daniela Adolf Employee of: Employee of StatConsult and may own stock or options, Carsten Holland Employee of: Employee of AbbVie and may own stock or options, Rouven Hecht Employee of: Employee of AbbVie and may own stock or options, Alexander Roessler Employee of: Employee of AbbVie and may own stock or options, Kirsten Famulla Employee of: Employee of AbbVie and may own stock or options, Klaus Krueger Grant/research support from: AbbVie, Biogen, BMS, Celltrion, Gilead, Hexal, Janssen, Lilly, Medac, MSD, Novartis, Pfizer, Roche, and UCB.

Background SIP smart ER is a 6-month evidenced-based, multi-component behavioral intervention that targets sugar-sweetened beverages among adults. It consists of three in-person group classes, one teach-back call, and 11 automated phone calls. Given SIP smart ER’s previously demonstrated effectiveness, understanding its adoption, implementation, and potential for integration within a system that reaches health disparate communities is important to enhance its public health impact. During this pilot dissemination and implementation trial, SIP smart ER was delivered by trained staff from local health districts (delivery agents) in rural, Appalachian Virginia. SIP smart ER’s execution was supported by consultee-centered implementation strategies. Methods In this mixed-methods process evaluation, adoption and implementation indicators of the program and its implementation strategy (e.g., fidelity, feasibility, appropriateness, acceptability) were measured using tracking logs, delivery agent surveys and interviews, and fidelity checklists. Quantitative data were analyzed with descriptive statistics. Qualitative data were inductively coded. Results Delivery agents implemented SIP smart ER to the expected number of cohorts ( n  = 12), recruited 89% of cohorts, and taught 86% of expected small group classes with > 90% fidelity. The planned implementation strategies were also executed with high fidelity. Delivery agents completing the two-day training, pre-lesson meetings, fidelity checklists, and post-lesson meetings at rates of 86, 75, 100, and 100%, respectively. Additionally, delivery agents completed 5% ( n  = 3 of 66) and 10% ( n  = 6 of 59) of teach-back and missed class calls, respectively. On survey items using 6-point scales, delivery agents reported, on average, higher feasibility, appropriateness, and acceptability related to delivering the group classes (range 4.3 to 5.6) than executing missed class and teach-back calls (range 2.6 to 4.6). They also, on average, found the implementation strategy activities to be helpful (range 4.9 to 6.0). Delivery agents identified strengths and weakness related to recruitment, lesson delivery, call completion, and the implementation strategy. Conclusions In-person classes and the consultee-centered implementation strategies were viewed as acceptable, appropriate, and feasible and were executed with high fidelity. However, implementation outcomes for teach-back and missed class calls and recruitment were not as strong. Findings will inform the future full-scale dissemination and implementation of SIP smart ER, as well as other evidence-based interventions, into rural health districts as a means to improve population health.

The purpose of this systematic review is to evaluate the prevalence of disordered eating and eating disorders among women seeking fertility treatment.Observational studies were searched in Ovid MEDLINE, Web of Science, Embase, and PsycInfo. Studies published prior to September 2020 when the search was conducted were considered. Inclusion criteria included (1) original and empirical research, (2) published in a peer-reviewed journal, and (3) reported on disordered eating among women seeking fertility treatment in the sample or reported on prevalence of eating disorders among women seeking fertility treatment in the sample. Independent screening of abstracts was conducted by two authors (LH and AH). Ten studies met the inclusion criteria. Sample size, study location, measures, and results for each study in this review were reported.Among women pursuing fertility treatment, rates of current eating disorders ranged from 0.5 to 16.7%, while past eating disorder prevalence rates ranged from 1.4 to 27.5%. Current anorexia nervosa or bulimia nervosa was reported by up to 2% and 10.3% of women, respectively, while history of anorexia nervosa or bulimia nervosa was reported by up to 8.5% and 3.3% of women, respectively. Binge eating disorder or other eating disorders were reported by up to 18.5% and 9.1% of women, respectively. Disordered eating pathology was endorsed by 1.6 to 48% of women seeking fertility treatment. Endorsement of pathological eating attitudes was generally higher among women seeking fertility treatment with current or past eating disorders as compared to community samples, with the exception of dietary restraint. Rates of current and past eating disorders are higher among women seeking fertility treatment than in the general population. Providers treating women with infertility should be cognizant of these prevalence rates and consider screening for eating pathology in their patients as this may contribute to their likelihood of successful conception and/or subsequent pregnancy outcomes.

Building footprint data from National Mapping and Cadastral Agencies are available in Germany for 7 years as a uniform, nation-wide geospatial data set and are updated annually. These multi-temporal building data sets can form the basis for the application of change detection techniques to derive national figures on dynamics in the building stock. Since these building data sets have only been built up in recent years, it is necessary to distinguish real changes from false changes. This is done by applying vector geometry-based operations and statistical analyses, which are presented in this article. Furthermore, by the additional use of the raster dataset Copernicus – European Settlement Map (classified, resolution 2.5 m) it is approximately possible to estimate whether it is a correct change or not. The advantage of this approach is that large-scale comparable results can be derived simply and quickly based on uniform basic data.

Urban green spaces (UGSs) can provide important ecosystem services for citizens and their well-being. To make use of these services according to UGS user demands, urban residents, tourists, and city administrations should know where UGSs are located, what qualities they have and how to reach them on convenient routes. This paper presents a novel digital infrastructure which combines and fuses different data to map UGSs and their qualities, and makes this information available in a web app. The interactive information service of the app aims to support citizens to explore and search for suitable UGSs and to provide routing options to reach them based on their preferences. Via implicit and explicit feedback functions included in the app, further information on UGS users' preferences can be collected to enhance the overall knowledge basis, while respecting data privacy issues. The underlying data base consists primarily of open and volunteered geographic data, which allows for transferability to other cities. This paper describes the system design, its back-end and front-end components, as well as the process of development and deployment of the system in two pilot cities. Preliminary results of the piloting in the two cities are presented, focusing on user preferences for UGSs searches. The added value of the web app for city residents and the role of the newly gained knowledge for urban planning is discussed and reflected upon.

In this paper, a distributed computing framework that exploits high-performance compute clusters and employs a Distributed Multiple-Swarm Particle Swarm Optimization (DMSPSO) algorithm is proposed for solving two-point boundary-value problems in astrodynamics. The DMSPSO algorithm performs a search of the solution space by attempting to minimize the weighted sum of squares of the boundary condition residuals, generating many guesses for the unknown variables that nearly satisfy the boundary conditions. These guesses are then used to solve the boundary-value problem with a gradient-based algorithm that runs in parallel with the DMSPSO search. The proposed framework is applied to solve two different boundary-value problems in astrodynamics. The first is formulated to compute energy-optimal transfers between a Geostationary Transfer Orbit and an L1 halo orbit using the Calculus of Variations approach, and the second is formulated to compute periodic orbits in the Circular Restricted Three Body Problem model. It is demonstrated that the methodology provides a large speedup over a conventional Particle Swarm Optimization algorithm, can be applied to solve sensitive boundary value problems, and facilitates the discovery of many (if not all) solutions of a given two-point boundary-value problem.

Guided by the Cultural Theory of Risk (CTR), the present study examined the relationship between college students’ cultural worldviews and their climate change threat perception, knowledge levels, and likelihood of engaging in mitigation behaviors. Additionally, the study attempted to investigate the association between the greenhouse gas (GHG) emissions levels of college students’ home countries and their perceived threat of climate change. One-hundred fifty-one college students, representing eighteen countries, completed a survey assessing these variables. Pearson’s correlation analyses revealed a positive relationship between both individualism and hierarchy and college students’ climate change threat perception, knowledge levels, and mitigation behaviors. While a small and demographically skewed sample precluded a global analysis of the association between home country and threat perception, American and Indian respondents had no difference in their perceived threat of climate change. This study’s findings provide a more complete picture of the factors that influence college students’ climate change attitudes and behaviors as well as several implications for achieving more effective climate change communication among culturally diverse college students.

Thermal diffusivity of automotive grade SAE G3000 (d) gray cast iron has been measured as a function of graphite flake morphology, chemical composition and temperature. Cast iron samples used for this investigation were cut from “step block” castings designed to produce iron with different graphite flake morphologies resulting from different cooling rates. Samples were also machined from prototype and commercial brake rotors, as well as from a series of cast iron slugs with slightly varying compositions. Thermal diffusivity was measured at room and elevated temperatures via the flash technique. Graphite flake morphology of the various cast iron samples was quantified stereologically with image analysis techniques. Several geometric features of the graphite flake morphology were quantified. It was found that the thermal diffusivity of these gray cast irons increases with carbon equivalent and has a strong linear correlation to graphite flake length. For gray iron with the same chemical composition, a four fold increase in the graphite flake size results in a 50% increase in thermal diffusivity. Amongst the commercial rotors, room temperature thermal diffusivity varied from 0.156 to 0.200 cm2/s.

Over the 5-year period ending in 2018, 16 countries with a combined birth cohort of over 6 million infants requiring life-saving immunizations are scheduled to transition (graduate) from outside financial and technical support for a number of their essential vaccines. This support has been provided over the past decade by the GAVI Alliance. Will these 16 countries be able to continue to sustain these vaccination efforts? To address this issue, GAVI and its partners are supporting transition planning, entailing country assessments of readiness to graduate and intensive dialogue with national officials to ensure a smooth transition process. This approach was piloted in Bhutan, Republic of Congo, Georgia, Moldova and Mongolia in 2012. The pilot showed that graduating countries are highly heterogeneous in their capacity to assume responsibility for their immunization programmes. Although all possess certain strengths, each country displayed weaknesses in some of the following areas: budgeting for vaccine purchase, national procurement practices, performance of national regulatory agencies, and technical capacity for vaccine planning and advocacy. The 2012 pilot experience further demonstrated the value of transition planning processes and tools. As a result, GAVI has decided to continue with transition planning in 2013 and beyond. As the graduation process advances, GAVI and graduating countries should continue to contribute to global collective thinking about how developing countries can successfully end their dependence on donor aid and achieve self-sufficiency. Sur une période de cinq ans se terminant en 2018, seize pays connaissant une cohorte de naissances de plus de six millions d’enfants ayant besoin d’être vaccinés doivent effectuer une transition (graduation) vers un modèle d’autonomie technique et de financement pour un certain nombre de vaccins indispensables, et ce sans soutien extérieur. Au cours des dix dernières années, la Global Alliance for Vaccines and Immunization (GAVI) a assuré ce soutien. Ces seize pays serontils capables de maintenir durablement leurs efforts de vaccination? Pour répondre à cette problématique, GAVI et ses partenaires soutiennent des programmes de transition permettant une évaluation du degré de préparation de chaque pays à être éligible et de savoir si les représentants officiels sont prêts à un dialogue intensif afin que le processus se passe en douceur. Cette approche a été testée en 2012 au Bhoutan, au Congo, en Géorgie, en Moldavie et en Mongolie. Cette étude montre que ces pays sont hautement hétérogènes dans leur capacité à assumer la responsabilité de leurs programmes de vaccination. Bien qu’ils aient tous des points forts, chaque pays a montré une faiblesse dans un des domaines suivants: budgétisation de l’achat de vaccins, les pratiques existantes du marché public, l’efficacité des agences nationales de régulation et la capacité technique pour la planification et la mise en place d’un vaccin. L’étude pilote de 2012 a aussi permis de mettre en avant les processus de planification et les outils de transition. C’est ce qui a décidé GAVI à continuer le processus de transition pour l’année 2013 et pour les années à venir. Durant ce processus, GAVI et les pays sélectionnés doivent continuer de contribuer à une réflexion collective pour savoir comment les pays en développement peuvent en finir avec leur dépendance à l’aide humanitaire et arriver à l’autonomie. 到 2018 年为止， 16 个国家要在五年中从接受外部的资金和 技术支持来为总共超过六百万的婴儿提供生存必须的疫苗转 变为发展自己的疫苗。在过去十年中，全球疫苗和免疫联盟 （GAVI）一直提供这项支持。这 16 个国家是否能够继续维 持这些疫苗的接种？为了解决这个问题，GAVI 及其合作者 正在实施一项转变计划，为保证转变的顺利进行，对这些国 家进行了相关评估，并与政府官员进行了密集的对话。在 2012 年，这个方法首先在刚果、格鲁吉亚、摩尔多瓦和蒙 古进行了试点。试点的结果表明这些实施了渐变计划的国家 在他们自己承担免疫接种方面的能力有很大的差异。尽管各 有长处，每个国家都在以下方面显示出了不足：对购买疫苗 进行预算，国家采购的实施，国家监管机构的效果，对疫苗 计划和倡导的技术能力。 2012 年试点的经验进一步证明了 转变计划过程和工具的价值。因此，GAVI 决定在 2013 年以 及之后继续进行转变计划。随着转变的进行，GAVI 以及转 变国家应该继续为全球关于发展中国家如何能够成功结束依 靠援助实现自己自足的思考提供借鉴。 Durante el periodo de 5 años que termina en el 2018, 16 países con una cohorte de nacimientos combinada de más de 6 millones de niños que requieren inmunizaciones esenciales, están programados para una transición (graduación) de apoyo financiero externo y tecnológico para un número de sus vacunas esenciales. Este apoyo ha sido provisto desde la pasada década por la Alianza Global para Vacunas e Inmunización (GAVI). ¿Serán estos 16 países capaces de continuar sosteniendo estos esfuerzos de vacunación? A fin de abordar este tema, GAVI y sus socios están apoyando la planeación de la transición, lo cual incluye la valoración del país en relación a su aptitud para graduarse y diálogo intenso con funcionarios nacionales con el objeto de lograr un proceso de transición suave. Dicho enfoque fue intentado en Bután, República del Congo, Georgia, Moldavia y Mongolia en el 2012. Este programa piloto mostró que los países graduados son altamente heterogéneos en su capacidad para asumir la responsabilidad en sus programas de inmunización. Aunque todos poseen ciertas fortalezas, cada país mostró debilidades en algunas de las siguientes áreas: creación de presupuestos para la compra de vacunas, prácticas nacionales para la adquisición, desempeño de las agencias nacionales de regulaciones, y capacidad técnica para la planeación de vacunas y de apoyo. El experimento piloto del 2012 confirmó el valor de los procesos y herramientas de planeación para la transición. Como resultado, GAVI decidió continuar con la planificación de transición en el 2013 y más adelante. A medida que el proceso de graduación avanza, GAVI y los países graduados deberían continuar contribuyendo al pensamiento global colectivo acerca de cómo los países en vía de desarrollo pueden terminar en forma exitosa su dependencia en la ayuda de donantes y alcanzar su auto-suficiencia.