Quantitative Evidence for Revising the Definition of Primary Graft Dysfunction after Lung Transplant

RATIONALE: Primary graft dysfunction (PGD) is a form of acute lung injury that occurs after lung transplantation. The definition of PGD was standardized in 2005. Since that time, clinical practice has evolved, and this definition is increasingly used as a primary endpoint for clinical trials; therefore, validation is warranted. OBJECTIVES: We sought to determine whether refinements to the 2005 consensus definition could further improve construct validity. METHODS: Data from the Lung Transplant Outcomes Group multicenter cohort were used to compare variations on the PGD definition, including alternate oxygenation thresholds, inclusion of additional severity groups, and effects of procedure type and mechanical ventilation. Convergent and divergent validity were compared for mortality prediction and concurrent lung injury biomarker discrimination. MEASUREMENTS AND MAIN RESULTS: A total of 1,179 subjects from 10 centers were enrolled from 2007 to 2012. Median length of follow-up was 4 years (interquartile range = 2.4-5.9). No mortality differences were noted between no PGD (grade 0) and mild PGD (grade 1). Significantly better mortality discrimination was evident for all definitions using later time points (48, 72, or 48-72 hours; P < 0.001). Biomarker divergent discrimination was superior when collapsing grades 0 and 1. Additional severity grades, use of mechanical ventilation, and transplant procedure type had minimal or no effect on mortality or biomarker discrimination. CONCLUSIONS: The PGD consensus definition can be simplified by combining lower PGD grades. Construct validity of grading was present regardless of transplant procedure type or use of mechanical ventilation. Additional severity categories had minimal impact on mortality or biomarker discrimination

Las epistemologías críticas en la producción de conocimiento en Ciencia Política. Un estudio desde las trayectorias de docentes-investigadores de instituciones públicas

El presente proyecto pretendió aportar al estudio del desarrollo de la Ciencia Política en Argentina en el marco de la discusión iniciada por Giovanni Sartori, quien en el año 2004 cuestionó el status epistemológico- metodológico de la disciplina, dando inicio a una fructífera reflexión en torno a sus enfoques y paradigmas. En este marco, se sistematizaron y analizaron procesos de investigación concretos que, dentro del campo disciplinar, abrevan en diversas perspectivas epistemológicas críticas. Esto se llevó adelante a través de una serie de ejes de indagación orientados a analizar dichos procesos de modo transversal: 1- el reconocimiento de la posición del sujeto cognoscente como parte de la situación de investigación, 2- las articulaciones con sujetos y saberes extra-académicos en el proceso de construcción de conocimiento, 3- los vínculos con los espacios institucionales en los que se insertan las investigaciones y 4- las prácticas investigativas, académicas y pedagógicas concretas puestas en marcha en la producción de conocimiento. Estos ejes fueron abordados desde un enfoque cualitativo que combina el análisis documental de publicaciones científicas, con el análisis de trayectorias individuales y colectivas a través de entrevistas semiestructuradas a docentes investigadores de instituciones públicas.    ARK: http://id.caicyt.gov.ar/ark:/s22504559/n86d607b

Reducing nitrous oxide emissions by changing N fertiliser use from calcium ammonium nitrate (CAN) to urea based formulations

This research was financially supported under the National Development Plan, through the Research Stimulus Fund, administered by the Department of Agriculture, Food and the Marine (Grant numbers RSF10-/RD/SC/716 and RSF11S138) and from the Department of Agriculture and Rural Development (Ref: DARD Evidence and Innovation project 13/04/06) for Northern Ireland. The first author gratefully acknowledges funding received from the Teagasc Walsh Fellowship Scheme (Ref: 2012005).peer-reviewedThe accelerating use of synthetic nitrogen (N) fertilisers, to meet the world's growing food demand, is the primary driver for increased atmospheric concentrations of nitrous oxide (N2O). The IPCC default emission factor (EF) for N2O from soils is 1% of the N applied, irrespective of its form. However, N2O emissions tend to be higher from nitrate-containing fertilisers e.g. calcium ammonium nitrate (CAN) compared to urea, particularly in regions, which have mild, wet climates and high organic matter soils. Urea can be an inefficient N source due to NH3 volatilisation, but nitrogen stabilisers (urease and nitrification inhibitors) can improve its efficacy. This study evaluated the impact of switching fertiliser formulation from calcium ammonium nitrate (CAN) to urea-based products, as a potential mitigation strategy to reduce N2O emissions at six temperate grassland sites on the island of Ireland. The surface applied formulations included CAN, urea and urea with the urease inhibitor N-(n-butyl) thiophosphoric triamide (NBPT) and/or the nitrification inhibitor dicyandiamide (DCD). Results showed that N2O emissions were significantly affected by fertiliser formulation, soil type and climatic conditions. The direct N2O emission factor (EF) from CAN averaged 1.49% overall sites, but was highly variable, ranging from 0.58% to 3.81. Amending urea with NBPT, to reduce ammonia volatilisation, resulted in an average EF of 0.40% (ranging from 0.21 to 0.69%)-compared to an average EF of 0.25% for urea (ranging from 0.1 to 0.49%), with both fertilisers significantly lower and less variable than CAN. Cumulative N2O emissions from urea amended with both NBPT and DCD were not significantly different from background levels. Switching from CAN to stabilised urea formulations was found to be an effective strategy to reduce N2O emissions, particularly in wet, temperate grassland.Department of Agriculture and Rural Development for Northern IrelandTeagasc Walsh Fellowship ProgrammeDepartment of Agriculture, Food and the Marin

A Standardized Morpho-Functional Classification of the Planet’s Humipedons

It was time to take stock. We modified the humipedon classification key published in 2018 to make it easier and more practical. This morpho-functional taxonomy of the topsoil (humipedon) was only available in English; we also translated it into French and Italian. A standardized morphofunctional classification of humipedons (roughly the top 30–40 cm of soil: organic and organomineral surface horizons) would allow for a better understanding of the functioning of the soil ecosystem. This paper provides the founding principles of the classification of humipedon into humus systems and forms. With the recognition of a few diagnostic horizons, all humus systems can be determined. The humus forms that make up these humus systems are revealed by measuring the thicknesses of the diagnostic horizons. In the final part of the article, several figures represent the screenshots of a mobile phone or tablet application that allows for a fast recall of the diagnostic elements of the classification in the field. The article attempts to promote a standardized classification of humipedons for a global and shared management of soil at planet level

A standardized morpho-functional classification of the planet’s humipedons

It was time to take stock. We modified the humipedon classification key published in 2018 to make it easier and more practical. This morpho-functional taxonomy of the topsoil (humipedon) was only available in English; we also translated it into French and Italian. A standardized morphofunctional classification of humipedons (roughly the top 30–40 cm of soil: organic and organomineral surface horizons) would allow for a better understanding of the functioning of the soil ecosystem. This paper provides the founding principles of the classification of humipedon into humus systems and forms. With the recognition of a few diagnostic horizons, all humus systems can be determined. The humus forms that make up these humus systems are revealed by measuring the thicknesses of the diagnostic horizons. In the final part of the article, several figures represent the screenshots of a mobile phone or tablet application that allows for a fast recall of the diagnostic elements of the classification in the field. The article attempts to promote a standardized classification of humipedons for a global and shared management of soil at planet level

Clonal dynamics of BRAF-driven drug resistance in EGFR-mutant lung cancer

Activation of MAPK signaling via BRAF mutations may limit the activity of EGFR inhibitors in EGFR-mutant lung cancer patients. However, the impact of BRAF mutations on the selection and fitness of emerging resistant clones during anti-EGFR therapy remains elusive. We tracked the evolution of subclonal mutations by whole-exome sequencing and performed clonal analyses of individual metastases during therapy. Complementary functional analyses of polyclonal EGFR-mutant cell pools showed a dose-dependent enrichment of BRAF(V600E) and a loss of EGFR inhibitor susceptibility. The clones remain stable and become vulnerable to combined EGFR, RAF, and MEK inhibition. Moreover, only osimertinib/trametinib combination treatment, but not monotherapy with either of these drugs, leads to robust tumor shrinkage in EGFR-driven xenograft models harboring BRAF mutations. These data provide insights into the dynamics of clonal evolution of EGFR-mutant tumors and the therapeutic implications of BRAF(V600E) co-mutations that may facilitate the development of treatment strategies to improve the prognosis of these patients

Why The Automobile Has No Future: A Global Impact Analysis

An increasing number of people are beginning to understand the adverse impacts of the private car – and that the societal disadvantages of mass private car usage far outweigh the perceived individual benefits.  This report draws together, for the first time, the diverse adverse impacts of the car, in countries and cities globally, and also with a focus on trends in Germany. Discourses on travel from Frankfurt are also developed - to give an example of how different views on travel might be better understood and responded to in strategy making

Annals of Medicine / Fluoxetine normalizes disrupted light-induced entrainment, fragmented ultradian rhythms and altered hippocampal clock gene expression in an animal model of high trait anxiety- and depression-related behavior

Introduction Disturbances of circadian rhythms are a key symptom of mood and anxiety disorders. Selective serotonin reuptake inhibitors (SSRIs) - commonly used antidepressant drugs - also modulate aspects of circadian rhythmicity. However, their potential to restore circadian disturbances in depression remains to be investigated.Materials and methods The effects of the SSRI fluoxetine on genetically based, depression-related circadian disruptions at the behavioral and molecular level were examined using mice selectively bred for high anxiety-related and co-segregating depression-like behavior (HAB) and normal anxiety/depression behavior mice (NAB).Results The length of the circadian period was increased in fluoxetine-treated HAB as compared to NAB mice while the number of activity bouts and light-induced entrainment were comparable. No difference in hippocampal Cry2 expression, previously reported to be dysbalanced in untreated HAB mice, was observed, while Per2 and Per3 mRNA levels were higher in HAB mice under fluoxetine treatment.Discussion The present findings provide evidence that fluoxetine treatment normalizes disrupted circadian locomotor activity and clock gene expression in a genetic mouse model of high trait anxiety and depression. An interaction between the molecular mechanisms mediating the antidepressant response to fluoxetine and the endogenous regulation of circadian rhythms in genetically based mood and anxiety disorders is proposed.P 27520-B27(VLID)314239