The epistemological challenge of truth-subversion to the Liberal International Order

Truth-subversion practices, which populist leaders utilize for political domination, are a significant source of current pressure on the Liberal International Order (LIO). Truth-subversion practices include false speak (flagrant lying to subvert the concept of facts), double speak (intentional internal contradictions in speech to erode reason), and flooding (the emission of many messages into the public domain to create confusion). Aiming to destroy liberal truth ideals and practices, truth subversion weakens epistemological security; that is, the experience of orderliness and safety that results from people's and institutions’ shared understandings of their common-sense reality. It privileges baseless claims over fact-based opinions, thus creating communities of the like-minded between which communication becomes impossible. Truth subversion challenges the LIO's three key institutions: democracy, markets, and multilateralism. If truth-subversion practices prevail, societal polarization, inaccurate information, and emotional inflaming strain democracy and human rights protections. Markets that depend for their functioning on accurate information can falter, and multilateralism that relies on communication and reasoned consensus can decay. International relations (IR) scholarship has recognized knowledge production practices as a key feature underlying the LIO, but has not yet identified challenges to those practices as a threat for the LIO. We discuss what the discipline can do to alleviate its blind spots

Conclusion: Epistemic communities, world order, and the creation of a reflective research program

Este artículo se extrae de la revista International Organization, vol. 46, nº 1, Knowledge, Power and International Policy Coordination, invierno 1992, ps. 367-390 y ha sido traducido con permiso de la editorial MIT PressLas Relaciones Internacionales carecen de una teoría y un juego de explicaciones creíble sobre el origen de las instituciones internacionales, los intereses estatales y el comportamiento de los estados en condiciones de incertidumbre. En este volumen no sólo desarrollamos “estudios particulares que (…) pueden iluminar asuntos importantes en la política internacional,” sino que también ofrecemos un programa de investigación mediante el cual los estudiantes de política internacional pueden estudiar de modo empírico el papel de las ideas en las relaciones internacionalesAccording to this research program, international relations can be seen as an evolutionary process in which epistemic communities play meaningful roles as sources of policy innovation, channels by which these innovations diffuse internationally, and catalysts in the political and institutional processes leading to the selection of their shared goals. International cooperation and, indeed, the development of new world orders based on common meanings and understandings may thus depend on the extent to which nation-states apply their power on behalf of practices that epistemic communities may have helped create, diffuse, and perpetuat

Prácticas internacionales

En este artículo se aborda la política mundial a través de los lentes de sus diversas prácticas, que son definidas como actuaciones competentes. Estudiar Relaciones Internacionales (RI) desde la perspectiva de las prácticas internacionales promete tres avances clave. El primero implica que se puede entender la teoría de las RI y la política internacional mejor o de forma diferente. La política mundial puede ser concebida como estructurada por prácticas, las que dan significados a las acciones internacionales, hacen posible la interacción estratégica, y son reproducidas, cambiadas y reforzadas por las acciones e interacciones internacionales. Este enfoque ayuda a expandir la ontología de la política mundial, sirve como punto focal sobre el cual estructurar los debates de la teoría de RI, y puede ser usado como unidad de análisis que transciende el entendimiento tradicional de los niveles de análisis. Se ilustra qué es una práctica internacional revisando el trabajo seminal de Thomas Schelling sobre negociaciones. El segundo avance, con la ayuda de ilustraciones sobre prácticas de disuasión y control de armas durante la Guerra Fría y la pos-Guerra Fría, tales como seguridad cooperativa, muestra como las prácticas constituyen interacción estratégica y negociación de modo más general. Finalmente, desde la perspectiva de las prácticas se abre el camino a una innovadora y apasionante agenda de investigación que sugiere nuevas preguntas y puzzles, y lleva a revisar conceptos centrales de la disciplina, como el poder, la historia y la estrategi

Water vapor and the dynamics of climate changes

Water vapor is not only Earth's dominant greenhouse gas. Through the release of latent heat when it condenses, it also plays an active role in dynamic processes that shape the global circulation of the atmosphere and thus climate. Here we present an overview of how latent heat release affects atmosphere dynamics in a broad range of climates, ranging from extremely cold to extremely warm. Contrary to widely held beliefs, atmospheric circulation statistics can change non-monotonically with global-mean surface temperature, in part because of dynamic effects of water vapor. For example, the strengths of the tropical Hadley circulation and of zonally asymmetric tropical circulations, as well as the kinetic energy of extratropical baroclinic eddies, can be lower than they presently are both in much warmer climates and in much colder climates. We discuss how latent heat release is implicated in such circulation changes, particularly through its effect on the atmospheric static stability, and we illustrate the circulation changes through simulations with an idealized general circulation model. This allows us to explore a continuum of climates, constrain macroscopic laws governing this climatic continuum, and place past and possible future climate changes in a broader context.Comment: 22 pages, 11 figure

Key factors in simulating the equatorial Atlantic zonal sea surface temperature gradient in a coupled general circulation model

Causes of the coupled model bias in simulating the zonal sea surface temperature (SST) gradient in the equatorial Atlantic are examined in three versions of the same coupled general circulation model (CGCM) differing only in the cumulus convection scheme. One version of the CGCM successfully simulates the mean zonal SST gradient of the equatorial Atlantic, in contrast to the failure of the Coupled Model Intercomparison Project phase 3 models. The present analysis shows that key factors to be successful are high skills in simulating the meridional location of the Intertropical Convergence Zone, the precipitation over northern South America, and the southerly winds along the west coast of Africa associated with the West African monsoon in boreal spring. Model biases in the Pacific contribute to the weaker precipitation over northern South America. Uncoupled experiments with the atmospheric component further confirm the importance of remote influences on the development of the equatorial Atlantic bias. Key Points: The zonal SST gradient of the equatorial Atlantic is well simulated in a CGCM; Key factors for the realistic simulation of the Atlantic SST are presented; Remote forcing from the Pacific may contribute to the Atlantic SST bia

In vitro and in vivo effects of Pelargonium sidoides DC. root extract EPs® 7630 and selected constituents against SARS-CoV-2 B.1, Delta AY.4/AY.117 and Omicron BA.2

The occurrence of immune-evasive SARS-CoV-2 strains emphasizes the importance to search for broad-acting antiviral compounds. Our previous in vitro study showed that Pelargonium sidoides DC. root extract EPs® 7630 has combined antiviral and immunomodulatory properties in SARS-CoV-2-infected human lung cells. Here we assessed in vivo effects of EPs® 7630 in SARS-CoV-2-infected hamsters, and investigated properties of EPs® 7630 and its functionally relevant constituents in context of phenotypically distinct SARS-CoV-2 variants. We show that EPs® 7630 reduced viral load early in the course of infection and displayed significant immunomodulatory properties positively modulating disease progression in hamsters. In addition, we find that EPs® 7630 differentially inhibits SARS-CoV-2 variants in nasal and bronchial human airway epithelial cells. Antiviral effects were more pronounced against Omicron BA.2 compared to B.1 and Delta, the latter two preferring TMPRSS2-mediated fusion with the plasma membrane for cell entry instead of receptor-mediated low pH-dependent endocytosis. By using SARS-CoV-2 Spike VSV-based pseudo particles (VSVpp), we confirm higher EPs® 7630 activity against Omicron Spike-VSVpp, which seems independent of the serine protease TMPRSS2, suggesting that EPs® 7630 targets endosomal entry. We identify at least two molecular constituents of EPs® 7630, i.e., (−)-epigallocatechin and taxifolin with antiviral effects on SARS-CoV-2 replication and cell entry. In summary, our study shows that EPs® 7630 ameliorates disease outcome in SARS-CoV-2-infected hamsters and has enhanced activity against Omicron, apparently by limiting late endosomal SARS-CoV-2 entry

Phase 1-2a multicenter dose-escalation study of ezatiostat hydrochloride liposomes for injection (Telintra®, TLK199), a novel glutathione analog prodrug in patients with myelodysplastic syndrome

<p>Abstract</p> <p>Background</p> <p>Ezatiostat hydrochloride liposomes for injection, a glutathione S-transferase P1-1 inhibitor, was evaluated in myelodysplastic syndrome (MDS). The objectives were to determine the safety, pharmacokinetics, and hematologic improvement (HI) rate. Phase 1-2a testing of ezatiostat for the treatment of MDS was conducted in a multidose-escalation, multicenter study. Phase 1 patients received ezatiostat at 5 dose levels (50, 100, 200, 400 and 600 mg/m²) intravenously (IV) on days 1 to 5 of a 14-day cycle until MDS progression or unacceptable toxicity. In phase 2, ezatiostat was administered on 2 dose schedules: 600 mg/m²IV on days 1 to 5 or days 1 to 3 of a 21-day treatment cycle.</p> <p>Results</p> <p>54 patients with histologically confirmed MDS were enrolled. The most common adverse events were grade 1 or 2, respectively, chills (11%, 9%), back pain (15%, 2%), flushing (19%, 0%), nausea (15%, 0%), bone pain (6%, 6%), fatigue (0%, 13%), extremity pain (7%, 4%), dyspnea (9%, 4%), and diarrhea (7%, 4%) related to acute infusional hypersensitivity reactions. The concentration of the primary active metabolites increased proportionate to ezatiostat dosage. Trilineage responses were observed in 4 of 16 patients (25%) with trilineage cytopenia. Hematologic Improvement-Erythroid (HI-E) was observed in 9 of 38 patients (24%), HI-Neutrophil in 11 of 26 patients (42%) and HI-Platelet in 12 of 24 patients (50%). These responses were accompanied by improvement in clinical symptoms and reductions in transfusion requirements. Improvement in bone marrow maturation and cellularity was also observed.</p> <p>Conclusion</p> <p>Phase 2 studies of ezatiostat hydrochloride liposomes for injection in MDS are supported by the tolerability and HI responses observed. An oral formulation of ezatiostat hydrochloride tablets is also in phase 2 clinical development.</p> <p>Trial Registration</p> <p>Clinicaltrials.gov: NCT00035867</p

A modeling study of the response of Asian summertime climate to the largest geologic forcings of the past 50 Ma

The modern Asian summer monsoon is known to be affected by the modern continental geometry, orography, atmospheric composition, interglacial climate state, and orbital configuration. All of these factors, however, have undergone substantial changes since the Indian and Asian continents collided 50 million years ago. Within the framework of one general circulation model we evaluate the relative importance of each of these factors for the spatial patterns of summertime climate fields and precipitation‐weighted 18O. We find that the continental‐scale structure of the monsoon circulation remains robust, but there are important impacts on local environmental conditions. The largest differences in climate are associated with changes in orbital configuration and topography because of how those factors influence local gradients in the summer climate variables. Finally, model calculations are consistent with the modern understanding of monsoon dynamics in which the strength of the circulation and the distribution of rainfall are tightly coupled to the spatial patterns of low‐level moist static energy and upper tropospheric temperature.Key PointsGeological changes in the Cenozoic have changed summertime climate in AsiaThe continental‐scale structure of the summer monsoon circulation remains robustLarge local climate changes occur, with insolation and local topography having the largest impactsPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/122412/1/jgrd52906.pd

Challenges in quantifying changes in the global water cycle

Human influences have likely already impacted the large-scale water cycle but natural variability and observational uncertainty are substantial. It is essential to maintain and improve observational capabilities to better characterize changes. Understanding observed changes to the global water cycle is key to predicting future climate changes and their impacts. While many datasets document crucial variables such as precipitation, ocean salinity, runoff, and humidity, most are uncertain for determining long-term changes. In situ networks provide long time-series over land but are sparse in many regions, particularly the tropics. Satellite and reanalysis datasets provide global coverage, but their long-term stability is lacking. However, comparisons of changes among related variables can give insights into the robustness of observed changes. For example, ocean salinity, interpreted with an understanding of ocean processes, can help cross-validate precipitation. Observational evidence for human influences on the water cycle is emerging, but uncertainties resulting from internal variability and observational errors are too large to determine whether the observed and simulated changes are consistent. Improvements to the in situ and satellite observing networks that monitor the changing water cycle are required, yet continued data coverage is threatened by funding reductions. Uncertainty both in the role of anthropogenic aerosols, and due to large climate variability presently limits confidence in attribution of observed changes