Patient preferences for palliative treatment of locally advanced or metastatic gastric cancer and adenocarcinoma of the gastroesophageal junction: a choice-based conjoint analysis study from Germany

Background: Decisions on palliative chemotherapy (CT) for locally advanced or metastatic gastric cancer (mGC) require trade-offs between potential benefits and risks for patients. Healthcare providers and payers agree that patient-preferences should be considered. We conducted a choice-based conjoint (CBC) analysis study in pre-treated patients from Germany with mGC or locally advanced or metastatic adenocarcinoma of the gastroesophageal junction (mGEJ-Ca), to evaluate their preferences when hypothetically selecting a CT regimen. Methods: German oncologists and gastroenterologists were contacted to identify patients with mGC or mGEJ-Ca who had completed ≥2 cycles of palliative CT in first or later lines of therapy (CT ongoing or complete). The primary objective was to quantify patient preferences for palliative CT by CBC analysis. Six in-depth qualitative interviews identified 3 attributes: treatment tolerability, quality of life in terms of ability of self-care, and additional survival benefit. The CBC matrix was constructed with 4 factor levels per attribute and each participant was presented with 15 different iterations of these levels. A minimum of 50 participants was needed. Consenting patients completed the CBC survey, choosing systematically among profiles. CBC models were estimated by multinomial logistic regression (MLR) and hierarchical Bayesian (HB) analysis. Estimates of importance for each attribute and factor-level were calculated. Results: Fifty-five patients participated in the CBC survey (78.2% male, median age 63 years, 81.8% currently receiving CT). Across this sample, low treatment toxicity was ranked highest (44.6% relative importance, MLR analysis), followed by ability to self-care (32.3%), and an additional survival benefit of up to 3 months (3 months 23.1%, 2 months 18.3%, 1 month 11.2%). The MLR analysis showed high validity (certainty 37.9%, chi square p < 0.01, root-likelihood 0.505). The HB analysis yielded similar results. Conclusions: Patients’ preferences related to a new hypothetical palliative CT of mGC or mGEJ-Ca can be assessed by CBCanalysis. Although in real-life, patients initially need to decide on CT before they have any experience, and patients’ varied experiences with CT will have impacted specific responses, low toxicity and self-care ability were considered as most important by this group of patients with mGC or mGEJ-Ca

XCO2_{2} retrieval for GOSAT and GOSAT-2 based on the FOCAL algorithm

Since 2009, the Greenhouse gases Observing SATellite (GOSAT) has performed radiance measurements in the near-infrared (NIR) and shortwave infrared (SWIR) spectral region. From February 2019 onward, data from GOSAT-2 have also been available. We present the first results from the application of the Fast atmOspheric traCe gAs retrievaL (FOCAL) algorithm to derive column-averaged dry-air mole fractions of carbon dioxide (XCO2) from GOSAT and GOSAT-2 radiances and their validation. FOCAL was initially developed for OCO-2 XCO2 retrievals and allows simultaneous retrievals of several gases over both land and ocean. Because FOCAL is accurate and numerically very fast, it is currently being considered as a candidate algorithm for the forthcoming European anthropogenic CO2 Monitoring (CO2M) mission to be launched in 2025. We present the adaptation of FOCAL to GOSAT and discuss the changes made and GOSAT specific additions. This particularly includes modifications in pre-processing (e.g. cloud detection) and post-processing (bias correction and filtering). A feature of the new application of FOCAL to GOSAT and GOSAT-2 is the independent use of both S- and P-polarisation spectra in the retrieval. This is not possible for OCO-2, which measures only one polarisation direction. Additionally, we make use of GOSAT\u27s wider spectral coverage compared to OCO-2 and derive not only XCO2, water vapour (H2O), and solar-induced fluorescence (SIF) but also methane (XCH4), with the potential for further atmospheric constituents and parameters like semi-heavy water vapour (HDO). In the case of GOSAT-2, the retrieval of nitrous oxide (XN2O) and carbon monoxide (CO) may also be possible. Here, we concentrate on the new FOCAL XCO2 data products. We describe the generation of the products as well as applied filtering and bias correction procedures. GOSAT-FOCAL XCO2 data have been produced for the time interval 2009 to 2019. Comparisons with other independent GOSAT data sets reveal agreement of long-term temporal variations within about 1 ppm over 1 decade; differences in seasonal variations of about 0.5 ppm are observed. Furthermore, we obtain a station-to-station bias of the new GOSAT-FOCAL product to the ground-based Total Carbon Column Observing Network (TCCON) of 0.56 ppm with a mean scatter of 1.89 ppm. The GOSAT-2-FOCAL XCO2 product is generated in a similar way as the GOSAT-FOCAL product, but with adapted settings. All GOSAT-2 data until the end of 2019 have been processed. Because of this limited time interval, the GOSAT-2 results are considered to be preliminary only, but first comparisons show that these data compare well with the GOSAT-FOCAL results and also TCCON

Benchmark of gyrokinetic, kinetic MHD and gyrofluid codes for the linear calculation of fast particle driven TAE dynamics

Fast particles in fusion plasmas may drive Alfvén modes unstable leading to fluctuations of the internal electromagnetic fields and potential loss of particles. Such instabilities can have an impact on the performance and the wall-load of machines with burning plasmas such as ITER. A linear benchmark for a toroidal Alfvén eigenmode (TAE) is done with 11 participating codes with a broad variation in the physical as well as the numerical models. A reasonable agreement of around 20% has been found for the growth rates. Also, the agreement of the eigenfunctions and mode frequencies is satisfying. However, they are found to depend strongly on the complexity of the used model

Resilience trinity: safeguarding ecosystem functioning and services across three different time horizons and decision contexts

Ensuring ecosystem resilience is an intuitive approach to safeguard the functioning of ecosystems and hence the future provisioning of ecosystem services (ES). However, resilience is a multi-faceted concept that is difficult to operationalize. Focusing on resilience mechanisms, such as diversity, network architectures or adaptive capacity, has recently been suggested as means to operationalize resilience. Still, the focus on mechanisms is not specific enough. We suggest a conceptual framework, resilience trinity, to facilitate management based on resilience mechanisms in three distinctive decision contexts and time-horizons: i) reactive, when there is an imminent threat to ES resilience and a high pressure to act, ii) adjustive, when the threat is known in general but there is still time to adapt management, and iii) provident, when time horizons are very long and the nature of the threats is uncertain, leading to a low willingness to act. Resilience has different interpretations and implications at these different time horizons, which also prevail in different disciplines. Social ecology, ecology, and engineering are often implicitly focussing on provident, adjustive, or reactive resilience, respectively, but these different notions and of resilience and their corresponding social, ecological, and economic trade-offs need to be reconciled. Otherwise, we keep risking unintended consequences of reactive actions, or shying away from provident action because of uncertainties that cannot be reduced. The suggested trinity of time horizons and their decision contexts could help ensuring that longer-term management actions are not missed while urgent threats to ES are given priority

Verification and validation of integrated simulation of energetic particles in fusion plasmas

This paper reports verification and validation of linear simulations of Alfvén eigenmodes in the current ramp phase of DIII-D L-mode discharge #159243 using gyrokinetic, gyrokinetic-MHD hybrid, and eigenvalue codes. Using a classical fast ion profile, all simulation codes find that reversed shear Alfvén eigenmodes (RSAE) are the dominant instability. The real frequencies from all codes have a coefficient of variation of less than 5% for the most unstable modes with toroidal mode number n  =  4 and 5. The simulated RSAE frequencies agree with experimental measurements if the minimum safety factor is adjusted, within experimental errors. The simulated growth rates exhibit greater variation, and simulations find that pressure gradients of thermal plasmas make a significant contribution to the growth rates. Mode structures of the dominant modes agree well among all codes. Moreover, using a calculated fast ion profile that takes into account the diffusion by multiple unstable modes, a toroidal Alfvén eigenmode (TAE) with n  =  6 is found to be unstable in the outer edge, consistent with the experimental observations. Variations of the real frequencies and growth rates of the TAE are slightly larger than those of the RSAE. Finally, electron temperature fluctuations and radial phase shifts from simulations show no significant differences with the experimental data for the strong n  =  4 RSAE, but significant differences for the weak n  =  6 TAE. The verification and validation for the linear Alfvén eigenmodes is the first step to develop an integrated simulation of energetic particles confinement in burning plasmas incorporating multiple physical processes

Demonstration of reduced neoclassical energy transport in Wendelstein 7-X

Research on magnetic confinement of high-temperature plasmas has the ultimate goal of harnessing nuclear fusion for the production of electricity. Although the tokamak1 is the leading toroidal magnetic-confinement concept, it is not without shortcomings and the fusion community has therefore also pursued alternative concepts such as the stellarator. Unlike axisymmetric tokamaks, stellarators possess a three-dimensional (3D) magnetic field geometry. The availability of this additional dimension opens up an extensive configuration space for computational optimization of both the field geometry itself and the current-carrying coils that produce it. Such an optimization was undertaken in designing Wendelstein 7-X (W7-X)2, a large helical-axis advanced stellarator (HELIAS), which began operation in 2015 at Greifswald, Germany. A major drawback of 3D magnetic field geometry, however, is that it introduces a strong temperature dependence into the stellarator’s non-turbulent ‘neoclassical’ energy transport. Indeed, such energy losses will become prohibitive in high-temperature reactor plasmas unless a strong reduction of the geometrical factor associated with this transport can be achieved; such a reduction was therefore a principal goal of the design of W7-X. In spite of the modest heating power currently available, W7-X has already been able to achieve high-temperature plasma conditions during its 2017 and 2018 experimental campaigns, producing record values of the fusion triple product for such stellarator plasmas3,4. The triple product of plasma density, ion temperature and energy confinement time is used in fusion research as a figure of merit, as it must attain a certain threshold value before net-energy-producing operation of a reactor becomes possible1,5. Here we demonstrate that such record values provide evidence for reduced neoclassical energy transport in W7-X, as the plasma profiles that produced these results could not have been obtained in stellarators lacking a comparably high level of neoclassical optimization