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Uncertainty assessment is a cornerstone in model-based health economic evaluations (HEEs) that inform reimbursement decisions. No comprehensive overview of available uncertainty assessment methods currently exists. We aimed to review methods for uncertainty assessment for use in model-based HEEs, by conducting a snowballing review. We categorised all methods according to their stage of use relating to uncertainty assessment (identification, analysis, communication). Additionally, we classified identification methods according to sources of uncertainty, and subdivided analysis and communication methods according to their purpose. The review identified a total of 80 uncertainty methods: 30 identification, 28 analysis, and 22 communication methods. Uncertainty identification methods exist to address uncertainty from different sources. Most identification methods were developed with the objective to assess related concepts such as validity, model quality, and relevance. Almost all uncertainty analysis and communication methods required uncertainty to be quantified and inclusion of uncertainties in probabilistic analysis. Our review can help analysts and decision makers in selecting uncertainty assessment methods according to their aim and purpose of the assessment. We noted a need for further clarification of terminology and guidance on the use of (combinations of) methods to identify uncertainty and related concepts such as validity and quality. A key finding is that uncertainty assessment relies heavily on quantification, which may necessitate increased use of expert elicitation and/or the development of methods to assess unquantified uncertainty.

Contains fulltext : 290745.pdf (Publisher’s version ) (Open Access) The National Institute for Health and Care Excellence invited the manufacturer (Galapagos) of filgotinib (Jyseleca(®)), as part of the Single Technology Appraisal process, to submit evidence for the clinical effectiveness and cost effectiveness of filgotinib for treating moderately to severely active ulcerative colitis in adults who have had an inadequate response, loss of response or were intolerant to a previous biologic agent or conventional therapy. Kleijnen Systematic Reviews Ltd, in collaboration with Maastricht University Medical Centre+, was commissioned to act as the independent Evidence Review Group. This paper summarises the company submission, presents the Evidence Review Group's critical review on the clinical and cost-effectiveness evidence in the company submission, highlights the key methodological considerations and describes the development of the National Institute for Health and Care Excellence guidance by the Appraisal Committee. The company submission included one relevant study for the comparison of filgotinib versus placebo: the SELECTION trial. As there was no head-to-head evidence with any of the comparators, the company performed two separate network meta-analyses, one for the biologic-naïve population and one for the biologic-experienced population, and for both the induction and maintenance phases. The Evidence Review Group questioned the validity of the maintenance network meta-analysis because it assumed all active treatments to be comparators in this phase, which is not in line with clinical practice. The economic analysis used a number of assumptions that introduced substantial uncertainty, which could not be fully explored, for instance, the assumption that a risk of loss of response would be independent of health state and constant over time. Company and Evidence Review Group results indicate that at its current price, and disregarding confidential discounts for comparators and subsequent treatments, filgotinib dominates some comparators (golimumab and adalimumab in the company base case, all but intravenous and subcutaneous vedolizumab in the Evidence Review Group's base case) in the biologic-naïve population. In the biologic-experienced population, filgotinib dominates all comparators in both the company and the Evidence Review Group's base case. Results should be interpreted with caution as some important uncertainties were not included in the modelling. These uncertainties were mostly centred around the maintenance network meta-analysis, loss of response, health-related quality-of-life estimates and modelling of dose escalation. The National Institute for Health and Care Excellence recommended filgotinib within its marketing authorisation, as an option for treating moderately to severely active ulcerative colitis in adults when conventional or biological treatment cannot be tolerated, or if the disease has not responded well enough or has stopped responding to these treatments, and if the company provides filgotinib according to the commercial arrangement.

The USDA Forest Service (USFS) is increasingly turning to partnership tools such as stewardship agreements (SAs) to accomplish land management objectives. In these arrangements, nonagency partners (partners) often bring resources, capabilities, and preferences that can influence management processes and activities. We explored the nature of partner influence in SAs through interviews with USFS and partner staff in four SA case studies in Arizona, California, and New Mexico. Interviewees perceived that partners influenced project prioritization; implementation pace, scope, and approach; and SA participants’ ways of working. Influence was linked to partners’ involvement in SA project selection; contribution of resources, expertise, and capabilities; and assumption of some project implementation responsibilities. USFS-partner relationships also appeared to encourage partnership-oriented approaches beyond the original project. Our research suggests SA partners are uniquely influential in the implementation of USFS management activities and recommends additional exploration of SAs in the context of collaborative implementation.

Agroecology is gaining increasing attention in tropical regions as a solution to maintaining robust ecosystem services for rural communities and down-stream users. The incorporation of tree configurations into working landscapes is a specific agroecology practice, that to be effective, must be driven by regional values and preferences. In rural Costa Rica, we used a photo-based survey to determine landowner preferences for tree configurations that could be incorporated into landscape design on private property. We examined landowner motivations for having trees on private land, as well as community-identified barriers to maintaining tree cover. We found that landowners were very interested in the incorporation of large tree configurations (e.g., wide riparian buffer zones; large, forested patches) and that preferences did not vary significantly by demographics (respondent’s property size; income source). Respondents identified various regulating, supporting, and cultural ecosystem services as important motivating factors for maintaining trees on private land, whereas provisioning services and legal reasons were not as strong motivating factors. While preferred tree configurations supported the values that landowners identified as important (e.g., habitat provisioning), barriers may inhibit the actual implementation of such configurations, including limited space and financial resources. To overcome such barriers, results indicate that a shift may be needed within Costa Rica’s Payment for Ecosystem Service program to increase participation among small landholders interested in tree conservation. Increasing dialog with local communities can generate a deeper understanding of potential challenges and landowner interest in tree incorporation, which can then inform regional agroecology recommendations and policy.

The main heroines of the German heroic epic "The Song of the Nibelungs" are the Burgundian princess Kriemhild, who became the wife of the protagonist Siegfried, and the Icelandic heroic maiden Brunhild, whose hand Siegfried wins in a fierce battle in order to give Brunhild over to the Burgundian king in exchange for his lover’s hand. Jealousy, a sharp dispute about social status and personal hostility between the two heroines result in a fierce quarrel at the gate of the Worms Cathedral. In this key scene, one heroine blames the other for the alleged premarital loss of virginity and shows her rival a belt as an evidence. The acute, tense conflict of characters and wills, outlined in this scene, has long been of interest to writers and artists. The scene of Queens’ Quarrel has become the subject of numerous works of art. This article examines the peculiarities of female characters’ visualization: how their bodies, clothes, appearance are depicted in works of literature, fine arts and cinema. The article is richly provided with illustrations and figurative examples.

Over one-fourth of the world's land area is dedicated to agriculture, and these lands provide important ecosystem services (ES). Trees are a key component of agricultural ecosystems' ability to provide ES, especially in tropical regions. Agricultural landowners' evaluation of the ES provided by trees influences management decisions, impacting tree cover at large scales. Using a case study approach, we conducted semi-structured interviews with four types of agricultural landowners in southern Costa Rica to better understand how they value ES provided by trees. We used a socio-cultural valuation method, which revealed that landowners highly valued regulating and provisioning ES provided by trees and that the number and type of ES identified was influenced by the principle economic activity. Those farmers with larger amounts of forests on their properties more often identified cultural ES. The socio-cultural valuation methods revealed that respondents valued trees as wildlife habitat, coupling supporting and cultural services with both material (e.g., tourism) and non-material benefits (e.g., beauty). Few farmers in the study benefited from payment for ecosystem services programs, but the high value farmers placed on trees indicates there are other opportunities to increase tree cover on farms, such as promotion of live fencing and expanded riparian corridors. Results from this work can help improve conservation outcomes by shifting the focus of ecosystem service valuation to the needs and concerns of small-scale farmers in the development of outreach programs, management plans, and policies aimed at increasing tree cover on private lands in agricultural landscapes.

Siegfried and Hagen, the main characters of the German heroic epic "The Song of the Nibelungs", are still recognizable and culturally significant images. There are certain "ideal" conceptions about their physical appearance. These visualizations come from a long tradition of iconographic representation of the main characters of the great epic, formed by various texts and works of fine art. This article examines the main milestones of this iconographic tradition, starting from the period of classicism and romanticism. The author gives a brief history of illustrations of the epic and examines the worlds of Richard Wagner and his tetralogy "The Ring of the Nibelung". The author also analyzes the ideological attitudes behind the image of the bodies of Nibelung heroes in the Empire, the Weimar Republic and the Third Reich. The article is richly provided with illustrations and figurative examples.

Mixing ratios of the criteria air contaminant nitrogen dioxide (NOA new near-UV photolytic converter for measurement of the criteria pollutant nitrogen dioxide (NO2) in ambient air by NO-O3 chemiluminescence (CL) was characterized. Four mechanisms that generate interferences were identified and investigated experimentally: direct photolysis of nitrous acid, which occurred at a rate constant 6% that of NO2, thermal decomposition of PAN and N2O5, surface promoted chemistry involving nitric acid, and secondary chemistry involving NO in the tubing connecting the converter and CL analyzer. These interferences are predicted to occur in all NO2 P-CL systems but can be avoided by appropriate thermal management and operating at high flow rates.

The United States Forest Service 2012 Planning Rule prioritizes making lands resilient to climate change. Although researchers have investigated the history of “resilience” and its multiple interpretations, few have examined perceptions or experiences of resource staff tasked with implementing resilience. We interviewed Forest Service staff in the Southwestern Region to evaluate how managers and planners interpret resilience as an agency strategy, execution of resilience in management, and climate change’s impact on perception of resilience. Interviewees identified resilience as a main driver of agency response to land management but, when applying the concept, experienced barriers including ambiguity; scale; management specificity versus broad, adaptive landscape approach; and lack of metrics or examples. Interviewees found restoring ecosystem function to promote resilience while planning for future changed landscapes difficult. They desired landscape-scale collaboration to understand how to operationalize the resilience directive. Our findings revealed obstacles and opportunities for resilience in a managerial context.

Recent political ecology (PE) frameworks have evolved to identify power disparities that have consequences for human health and disease development. These power disparities can lead to unequal access to health information, natural resources (e.g. farmland, clean water), micronutrients, healthcare, and other elements necessary to maintain healthy bodies and reduce risk of disease. While many PE and political ecology of health and disease (PEHD) frameworks examine access in terms of limitations, few examples highlight effects from increased access to resources. This article uses a PEHD lens to examine how diets and health in rural Kédougou, Senegal are influenced by increased access to globalized foodstuffs and stigmatization of local foods and medicines. A better understanding of dietary decision-making is critical in understudied regions such as Senegal because West Africa has a rapidly expanding population and is projected to be among regions of the world that are most burdened with non-communicable diseases (NCD). We used qualitative methods to: 1) describe current and historic diets in Kédougou; 2) identify perceived changes about diet, health, and access to resources; and 3) understand what might be influencing these changes. Our article shows that increased access and limited access are interconnected because increased, regular access to globalized foods and medicines could factor into reduced access to local foods and medicines. We found that social context strongly influenced use of local forest foods and medicines, even leading to a gradual stigmatization of using these resources.

Holistic Management (HM) is a decision-making framework based on triple bottom line thinking and a proactive approach to managing complexity. Primarily associated with an approach to managing livestock, it has spurred long running and still unresolved debates in rangeland ecology and management. Less studied are the social, cultural, and psychological aspects of HM, which may hold the key to successful ecological outcomes. In this article, we describe the main tenets of HM as conceived by wildlife biologist Allan Savory and address the longstanding and unresolved controversy over its legitimacy. We then provide a meta-analysis that not only provides an up-to-date review of the multidisciplinary evidence and ongoing arguments about HM, but also provides a novel explanation for the controversy—that it is grounded in epistemic differences between disciplines associated with agricultural science that rule out any chance of resolution. We conclude that the way to resolve the controversy over HM is to research, in partnership with ranchers, rangeland social-ecological systems in more holistic, integrated ways. This can account for the full range of human experience, co-produce new knowledge, and contribute to social-ecological transformation.

Research has recognized that in addition to consumer–brand relationships, consumers are engaged in social networks of consumer-to-consumer interactions, which increasingly take place online through virtual brand communities. However, little attention has been paid to how consumer-to-consumer influence within virtual brand communities plays a role when brands behave badly. This research examines the role of network embeddedness, specifically network centrality and network density, and psychological ownership in consumer responses to a brand transgression. Across three studies of virtual brand communities and one of offline brand communities, we document an inherent conflict for those who occupy a central position within a brand community. Central consumers are more likely to punish the brand for the transgression, but centrality also leads to greater psychological ownership of the brand community and the brand, which makes consumers less likely to punish the brand. Psychological ownership also leads to a higher likelihood of helping the brand recover from the transgression, creating an additional conflict for central consumers. Network density resolves these conflicts by strengthening the negative relationship between psychological ownership and likelihood to punish the brand, but only in online brand communities where punishing and helping behaviors are more visible and more likely to act as reputational signals for the central consumer. This suggests that firms should encourage the formation of dense virtual brand communities and cultivate psychological ownership among central community members in order to protect themselves from negative consequences in the wake of a transgression.

Salts are important secondary components of the icy shells of outer-planet satellites. Salt hydrates formed from freezing brines may influence reflectivity and absorption of surface-penetrating radars. We compare new measurements of frozen mixtures of water and magnesium sulfate with those made by Pettinelli et al. (2016) and Grimm et al. (2008) . We find a high-frequency real dielectric constant of the hydrate endmember (meridianiite) of 4.9 ± 0.3 at −85 °C, within the error bounds derived by Pettinelli and colleagues. We confirm the existence of a dielectric relaxation in meridianiite, similar to the well-known response of ice but at higher frequency and with lower amplitude. However, the meridianiite relaxation is evident only at supereutectic concentrations and for a freezing history that maximizes annealing and partitioning of soluble impurities into the lattice. Dielectric relaxation is nonetheless important for radar sounding of Europa because it controls absorptive loss. Chloride is the most abundant ice-soluble impurity on Europa and will have the greatest impact on radar absorption, whether in ice or hydrates. Salt hydrates may generate reflectivity contrasts in surface-penetrating radar but are unlikely to be uniquely identified.

An aroma extract dilution analysis applied to the volatiles isolated from jackfruit ( Artocarpus heterophyllus Lam.) pulp by solvent extraction and solvent-assisted flavor evaporation resulted in the detection of 48 odorants with flavor dilution (FD) factors between 1 and ≥8192. Application of gas chromatography-olfactometry to static headspace samples revealed additional five highly volatile odorants. The structures of 44 out of the 53 detected odorants could be assigned. These 44 compounds were quantitated using stable isotopically substituted odorants as internal standards, and their odor activity values (OAVs) were calculated as the ratio of the natural concentrations in jackfruit pulp and the odor threshold values in water. High OAVs were in particular obtained for ethyl 3-methylbutanoate (74000), ethyl butanoate (1800), 3-methylbutanal (1500), and 2-methylpropanal (1400). An aroma model solution based on the natural concentrations of the 35 compounds for which OAVs > 1 had been calculated fully mimicked the characteristic jackfruit pulp aroma.

Over the past 15 years, the suicide rate among members of the U.S. armed forces has doubled, with the greatest increase observed among soldiers in the Army. This increasing rate is paralleled by a smaller increase in the general U.S. population, observed across both genders, in virtually every age group and in nearly every state. An empirical question exists: What is the extent or degree to which the suicide trend in the Army is unique to that service, relative to what is observed in the general U.S. population? The Army has typically attempted to address this question by standardizing the general population to look like the Army on demographic characteristics. However, given the rise in suicide rates over the past decade, the Army wanted to better understand whether standardization based solely on age and gender is enough. Expanding the characteristics on which the general population is standardized to match the Army could be useful to gain a better understanding of the suicide trends in the Army. However, such a change also brings with it some challenges, including the lack of readily available data in the general U.S. population. In addition, even an expanded set of characteristics still results in having a large number of unmeasured factors that cannot be included in this type of analysis. In this study, the authors explore how accounting for age, gender, race/ethnicity, time, marital status, and educational attainment affects suicide rate differences between soldiers and a comparable subset of the general U.S. population.

The aim of this letter to the editor is to provide a comprehensive summary of uncertainty assessment in Health Technology Assessment, with a focus on transferability to the setting of rare diseases. The authors of "TRUST4RD: tool for reducing uncertainties in the evidence generation for specialised treatments for rare diseases" presented recommendations for reducing uncertainty in rare diseases. Their article is of great importance but unfortunately suffers from a lack of references to the wider uncertainty in Health Technology Assessment and research prioritisation literature and consequently fails to provide a trusted framework for decision-making in rare diseases. In this letter to the editor we critique the authors' tool and provide pointers as to how their proposal can be strengthened. We present references to the literature, including our own tool for uncertainty assessment (TRUST; unrelated to the authors' research), apply TRUST to two assessments of orphan drugs in rare diseases and provide a broader perspective on uncertainty and risk management in rare diseases, including a detailed research agenda.

International audience; More than 85% of the 23 investigations developed by VEXAG are largely accomplished via a NF mission centered on a variable-altitude balloon (aerobot) supported by a science/comm orbiter. Circling Venus >15 times over ~90 days, the aerobot repeatedly visits 52-62 km alts as it semi-continuously samples a host of environmental & surface parameters.

Charles D. Edwards (Jet Propulsion Laboratory, California Institute of Technology). Co-Authors: 1. Vlada Stamenkovic Jet Propulsion Laboratory, California Institute of Technology; 2. Penelope Boston NASA Ames; 3. Kennda Lynch LPI/USRA … et al.

Bulletin of the AAS, 53 (4)

Venus Corona and Tessera Explorer (VeCaTEx) would use an aerobot to descend repeatedly beneath the dense clouds for imaging targeted area of the surface in the near infrared to address six of the prime investigations prioritized by VEXAG. The technologies needed could be matured during the next decade.

One objective of a lander mission to Jupiter’s icy moon Europa is to detect liquid water within 30 km as well as characterizing the subsurface ocean. In order to satisfy this objective, water within the ice shell must also be identified. Inductive electromagnetic (EM) methods are optimal for water detection on Europa because even a small fraction of dissolved salts will make water orders of magnitude more electrically conductive than the ice shell. Compared to induction studies by the Galileo spacecraft, measurements of higher-frequency ambient EM fields are necessary to resolve the shallower depths of intrashell water. Although these fields have been mostly characterized by prior missions, their unknown source structures and plasma properties do not allow EM sounding using a single surface magnetometer or the orbit-to-surface magnetic transfer function, respectively. Instead, broadband EM sounding can be accomplished from a single surface station using the magnetotelluric (MT) method, which measures horizontal electric fields as well as the three-component magnetic field. We have developed a prototype Europa Magnetotelluric Sounder (EMS) to meet the measurement requirements in the relevant thermal, vacuum, and radiation environment. EMS comprises central electronics, a fluxgate magnetometer on a mast, and three ballistically deployed electrodes to measure differences in surface electric potential. In this paper, we describe EMS development and testing as well as providing supporting information on the concept of operations and calculations on water detectability. EMS can uniquely determine the occurrence of intrashell water on Europa, providing important constraints on habitability.

The recent 2017 update of the World Health Organization classification of lymphomas has significant changes from the previous edition. Subtypes of large B cell lymphoma and related aggressive B cell lymphomas are addressed. Clinicopathological features of entities as related to morphology, immunophenotype, cell of origin, and molecular/genetic findings are reviewed with emphasis on changes or updates in findings. Specific subtypes addressed include: T cell/histiocyte-rich large B cell lymphoma, primary diffuse large B cell lymphoma (DLBCL) of the CNS, primary cutaneous DLBCL leg-type, EBV-positive DLBCL, NOS, DLBCL associated with chronic inflammation, primary mediastinal large B cell lymphoma, intravascular large B cell lymphoma, ALK-positive large B cell lymphoma, plasmablastic lymphoma, primary effusion lymphoma, HHV8-positive diffuse large B-cell lymphoma, NOS, Burkitt lymphoma, Burkitt-like lymphoma with 11q aberration, high-grade B cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, high grade B cell lymphoma, NOS, B cell lymphoma, unclassifiable, with features intermediate between DLBCL and classic Hodgkin lymphoma and large B cell lymphoma with IRF4 translocation. In addition, EBV positive mucocutaneous ulcer is addressed.

The surface of Mars has been well mapped and characterized, yet the subsurface — the most likely place to find signs of extant or extinct life and a repository of useful resources for human exploration — remains unexplored. In the near future this is set to change.

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