The Hall of Mirrors Perceptions and Misperceptions in the Congressional Foreign Policy Process

Explores several factors related to an inconsistency in the voting record by the U.S. Congress on foreign policy issues, compared with the position taken by the public, administration officials, and leaders in business, labor, media, and education

Peak event: the rise, crisis and potential decline of the Olympic Games and the World Cup

This paper tracks the growth of two of the largest tourist events: the Olympic Games and the Football World Cup, drawing on a dataset containing all events between 1964 and 2018. Overall, the size of the three events has grown about 60-fold over the past 50 years, thirteen times faster than world GDP. We identify an S-shaped growth curve and four different growth periods, with an emergent crisis phase in the late 2010s that may have brought us to ‘peak event’ – the point at which these events have reached their largest size. Outlining three different scenarios, we argue that the Olympics and the World Cup are at a critical bifurcation point, which also requires new bidding and hosting policies

Role of the Adiponectin Binding Protein, T-Cadherin (cdh13), in Pulmonary Responses to Subacute Ozone

Adiponectin, an adipose derived hormone with pleiotropic functions, binds to several proteins, including T-cadherin. We have previously reported that adiponectin deficient (Adipo−/−) mice have increased IL-17A-dependent neutrophil accumulation in their lungs after subacute exposure to ozone (0.3 ppm for 72 hrs). The purpose of this study was to determine whether this anti-inflammatory effect of adiponectin required adiponectin binding to T-cadherin. Wildtype, Adipo−/−, T-cadherin deficient (T-cad−/−), and bideficient (Adipo−/−/T-cad−/−) mice were exposed to subacute ozone or air. Compared to wildtype mice, ozone-induced increases in pulmonary IL-17A mRNA expression were augmented in T-cad−/− and Adipo−/− mice. Compared to T-cad−/− mice, there was no further increase in IL-17A in Adipo−/−/T-cad−/− mice, indicating that adiponectin binding to T-cadherin is required for suppression of ozone-induced IL-17A expression. Similar results were obtained for pulmonary mRNA expression of saa3, an acute phase protein capable of inducing IL-17A expression. Comparison of lung histological sections across genotypes also indicated that adiponectin attenuation of ozone-induced inflammatory lesions at bronchiolar branch points required T-cadherin. BAL neutrophils and G-CSF were augmented in T-cad−/− mice and further augmented in Adipo−/−/T-cad−/− mice. Taken together with previous observations indicating that augmentation of these moieties in ozone exposed Adipo−/− mice is partially IL-17A dependent, the results indicate that effects of T-cadherin deficiency on BAL neutrophils and G-CSF are likely secondary to changes in IL-17A, but that adiponectin also acts via T-cadherin independent pathways. Our results indicate that T-cadherin is required for the ability of adiponectin to suppress some but not all aspects of ozone-induced pulmonary inflammation

How stable are visions for protected area management? Stakeholder perspectives before and during a pandemic

Envisioning processes enable protected area managers to chart a course for future management to reach desired goals, but unexpected changes that could affect future visions are not usually considered. The global COVID-19 pandemic provided an opportunity to explore changes in stakeholder visions, the values that underpin the visions, and their perceptions of landscape changes and the underlying drivers (e.g. climate change, mass tourism and demographic trends).Through a mixed-methods approach in this post-evaluation study, we gathered comparative data on these issues from stakeholders in the Sierra de Guadarrama National Park, Spain, between July 2019 (pre-pandemic) and October 2020 (mid-pandemic).Our qualitative analysis demonstrates that pre-pandemic, differences in visions for protected area management were largely spurred by different perceptions of drivers of change, rather than differences in values or perceived landscape changes, which were similar across different vision themes.One year later, in the midst of the COVID-19 pandemic, the majority of stakeholders reported that their values, visions and perceptions of drivers did not change despite this large-scale disturbance. Of the 20%-30% of stakeholders that did report changes, visions generally shifted towards greater prioritization of biodiversity and nature conservation as a result of heightened perceptions of the impacts of drivers of change associated with an increase in the numbers of park visitors. These drivers included mass tourism, mountain recreation, lack of environmental awareness, and change in values and traditions.Our findings reinforce the importance of adaptive and inclusive management of protected areas, including enhancing transparency and communications regarding factors driving change in the landscape, and integration of local and traditional knowledge and stakeholder perceptions of changes and drivers. Furthermore, management plans integrating stakeholder values have the potential to stay relevant even in the face of wildcard events such as a pandemic.To enhance the relevancy of visions and scenarios in conservation and land-use planning, scenario planning methodologies should more strongly consider different potential disturbances and how drivers of change in the near and far future can be affected by wildcard events such as a pandemic. A free Plain Language Summary can be found within the Supporting Information of this article

Role of the Adiponectin Binding Protein, T-Cadherin (Cdh13), in Allergic Airways Responses in Mice

Adiponectin is an adipose derived hormone that declines in obesity. We have previously shown that exogenous administration of adiponectin reduces allergic airways responses in mice. T-cadherin (T-cad; Cdh13) is a binding protein for the high molecular weight isoforms of adiponectin. To determine whether the beneficial effects of adiponectin on allergic airways responses require T-cad, we sensitized wildtype (WT), T-cadherin deficient (T-cad−/−) and adiponectin and T-cad bideficient mice to ovalbumin (OVA) and challenged the mice with aerosolized OVA or PBS. Compared to WT, T-cad−/− mice were protected against OVA-induced airway hyperresponsiveness, increases in BAL inflammatory cells, and induction of IL-13, IL-17, and eotaxin expression. Histological analysis of the lungs of OVA-challenged T-cad−/− versus WT mice indicated reduced inflammation around the airways, and reduced mucous cell hyperplasia. Combined adiponectin and T-cad deficiency reversed the effects of T-cad deficiency alone, indicating that the observed effects of T-cad deficiency require adiponectin. Compared to WT, serum adiponectin was markedly increased in T-cad−/− mice, likely because adiponectin that is normally sequestered by endothelial T-cad remains free in the circulation. In conclusion, T-cad does not mediate the protective effects of adiponectin. Instead, mice lacking T-cad have reduced allergic airways disease, likely because elevated serum adiponectin levels act on other adiponectin signaling pathways

How stable are visions for protected area management? Stakeholder perspectives before and during a pandemic

Envisioning processes enable protected area managers to chart a course for future management to reach desired goals, but unexpected changes that could affect future visions are not usually considered. The global COVID-19 pandemic provided an opportunity to explore changes in stakeholder visions, the values that underpin the visions, and their perceptions of landscape changes and the underlying drivers (e.g. climate change, mass tourism and demographic trends). Through a mixed-methods approach in this post-evaluation study, we gathered comparative data on these issues from stakeholders in the Sierra de Guadarrama National Park, Spain, between July 2019 (pre-pandemic) and October 2020 (mid-pandemic). Our qualitative analysis demonstrates that pre-pandemic, differences in visions for protected area management were largely spurred by different perceptions of drivers of change, rather than differences in values or perceived landscape changes, which were similar across different vision themes. One year later, in the midst of the COVID-19 pandemic, the majority of stakeholders reported that their values, visions and perceptions of drivers did not change despite this large-scale disturbance. Of the 20%-30% of stakeholders that did report changes, visions generally shifted towards greater prioritization of biodiversity and nature conservation as a result of heightened perceptions of the impacts of drivers of change associated with an increase in the numbers of park visitors. These drivers included mass tourism, mountain recreation, lack of environmental awareness, and change in values and traditions. Our findings reinforce the importance of adaptive and inclusive management of protected areas, including enhancing transparency and communications regarding factors driving change in the landscape, and integration of local and traditional knowledge and stakeholder perceptions of changes and drivers. Furthermore, management plans integrating stakeholder values have the potential to stay relevant even in the face of wildcard events such as a pandemic. To enhance the relevancy of visions and scenarios in conservation and land-use planning, scenario planning methodologies should more strongly consider different potential disturbances and how drivers of change in the near and far future can be affected by wildcard events such as a pandemic. A free Plain Language Summary can be found within the Supporting Information of this article.Peer reviewe

Genomic resolution of a cold subsurface aquifer community provides metabolic insights for novel microbes adapted to high CO2 concentrations.

As in many deep underground environments, the microbial communities in subsurface high-CO2 ecosystems remain relatively unexplored. Recent investigations based on single-gene assays revealed a remarkable variety of organisms from little studied phyla in Crystal Geyser (Utah, USA), a site where deeply sourced CO2 -saturated fluids are erupted at the surface. To provide genomic resolution of the metabolisms of these organisms, we used a novel metagenomic approach to recover 227 high-quality genomes from 150 microbial species affiliated with 46 different phylum-level lineages. Bacteria from two novel phylum-level lineages have the capacity for CO2 fixation. Analyses of carbon fixation pathways in all studied organisms revealed that the Wood-Ljungdahl pathway and the Calvin-Benson-Bassham Cycle occurred with the highest frequency, whereas the reverse TCA cycle was little used. We infer that this, and selection for form II RuBisCOs, are adaptions to high CO2 -concentrations. However, many autotrophs can also grow mixotrophically, a strategy that confers metabolic versatility. The assignment of 156 hydrogenases to 90 different organisms suggests that H2 is an important inter-species energy currency even under gaseous CO2 -saturation. Overall, metabolic analyses at the organism level provided insight into the biochemical cycles that support subsurface life under the extreme condition of CO2 saturation

A Phase I, First-in-Human Study of GSK2849330, an Anti-HER3 Monoclonal Antibody, in HER3-Expressing Solid Tumors

Background GSK2849330, an anti-HER3 monoclonal antibody that blocks HER3/Neuregulin 1 (NRG1) signaling in cancer cells, is engineered for enhanced antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. This phase I, first-in-human, open-label study assessed the safety, pharmacokinetics (PK), pharmacodynamics, and preliminary activity of GSK2849330 in patients with HER3-expressing advanced solid tumors. Patients and Methods Patients with various tumor types were prospectively selected for HER3 expression by immunohistochemistry; a subset was also screened for NRG1 mRNA expression. In the dose-escalation phase, patients received GSK2849330 1.4-30 mg/kg every 2 weeks, or 3 mg/kg or 30 mg/kg weekly, intravenously (IV). In the dose-expansion phase, patients received 30 mg/kg GSK2849330 IV weekly. Results Twenty-nine patients with HER3-expressing cancers, of whom two expressed NRG1, received GSK2849330 (dose escalation: n = 18, dose expansion: n = 11). GSK2849330 was well tolerated. No dose-limiting toxicities were observed. The highest dose, of 30 mg/kg weekly, expected to provide full target engagement, was selected for dose expansion. Treatment-emergent adverse events (AEs) were mostly grade 1 or 2. The most common AEs were diarrhea (66%), fatigue (62%), and decreased appetite (31%). Dose-proportional plasma exposures were achieved, with evidence of HER3 inhibition in paired tissue biopsies. Of 29 patients, only 1 confirmed partial response, lasting 19 months, was noted in a patient with CD74-NRG1-rearranged non-small cell lung cancer (NSCLC). Conclusion GSK2849330 demonstrated a favorable safety profile, dose-proportional PK, and evidence of target engagement, but limited antitumor activity in HER3-expressing cancers. The exceptional response seen in a patient with CD74-NRG1-rearranged NSCLC suggests further exploration in NRG1-fusion-positive cancers. Implications for Practice This first-in-human study confirms that GSK2849330 is well tolerated. Importantly, across a variety of HER3-expressing advanced tumors, prospective selection by HER3/NRG1 expression alone was insufficient to identify patients who could benefit from treatment with this antibody-dependent cell-mediated cytotoxicity- and complement-dependent cytotoxicity-enhanced anti-HER3 antibody. The only confirmed durable response achieved was in a patient with CD74-NRG1-rearranged lung cancer. This highlights the potential utility of screening for NRG1 fusions prospectively across tumor types to enrich potential responders to anti-HER3 agents in ongoing trials

Inclusive conservation and the Post-2020 Global Biodiversity Framework : Tensions and prospects

Publisher Copyright: © 2022 The Author(s)The draft Post-2020 Global Biodiversity Framework commits to achievement of equity and justice outcomes and represents a “relational turn” in how we understand inclusive conservation. Although “inclusivity” is drawn on as a means to engage diverse stakeholders, widening the framing of inclusivity can create new tensions with regard to how to manage protected areas. We first offer a set of tensions that emerge in the light of the relational turn in biodiversity conservation. Drawing on global case examples applying multiple methods of inclusive conservation, we then demonstrate that, by actively engaging in the interdependent phases of recognizing hybridity, enabling conditions for reflexivity and partnership building, tensions can not only be acknowledged but softened and, in some cases, reframed when managing for biodiversity, equity, and justice goals. The results can improve stakeholder engagement in protected area management, ultimately supporting better implementation of global biodiversity targets.Peer reviewe