Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Mar Menor: una laguna singular y sensible. Evaluación científica de su estado.

Este libro recopila las aportaciones que equipos de investigación de la Universidad de Murcia, Universidad Politécnica de Cartagena, Instituto Geológico-Minero de España, Universidad de Alicante, el Instituto Español de Oceanografía y otros organismos hicieron en las Jornadas Científicas del Mar Menor, celebradas en diciembre de 2014.La información recogida en este libro se estructura en dos grandes bloques, uno de Biología y Ecología del Mar Menor (capítulos 1 al 8) y otro de Condiciones fisicoquímicas e impacto de actividades humanas en la laguna (capítulos 9 al 14). El primer bloque resume buena parte de los estudios ecológicos realizados en el Mar Menor, que han servido para mejorar su conocimiento y también para cambiar antiguas asunciones sobre la naturaleza y el funcionamiento de estos ecosistemas lagunares (Capítulo 1). El segundo capítulo muestra que esta laguna alberga en zonas someras de su perímetro hábitats fundamentales para mantener y conservar tanto especies migratorias como residentes, que es necesario conocer para paliar el impacto de las actividades humanas que les afectan. En este sentido la reducción de la carga de nutrientes y contaminantes orgánicos e inorgánicos que fluyen hacia el Mar Menor puede ayudar a preservar la laguna en mejores condiciones, bien sea tratando las escorrentías (plantas de tratamiento, humedales artificiales u otras técnicas) y recuperar este agua para uso agrícola o evitar su descarga en la laguna (Capítulo 3). Estas actuaciones serán clave para la conservación de especies emblemáticas como el caballito de mar (Capítulo 4) y reducir el impacto de las proliferaciones masivas de medusas que se producen en la laguna desde 1993 (Capítulo 5). En este mismo sentido los cambios acaecidos en la laguna han favorecido la incursión de invertebrados marinos alóctonos (Capítulo 6) y han afectado a la respuesta de la dinámica poblacional de las aves acuáticas a distintas escalas (Capítulo 7). Para completar este bloque se ofrece una perspectiva histórica de la importancia que ha tenido la investigación sobre acuicultura realizada en esta laguna, que ha servido de base para su gran desarrollo actual (Capítulo 8). El segundo bloque se inicia con una evaluación del origen y evolución del Mar Menor desde el punto de vista geológico, y evidencia su vulnerabilidad ante el deterioro que puede sufrir la desaparición de la barrera de cierre y/o su colmatación (Capítulo 9). En el Capítulo 10 se describe la relevancia que tiene la interacción de los acuíferos del Campo de Cartagena con la laguna, que se produce no sólo a nivel superficial sino también subterráneo. Esta interacción permite el acceso de nutrientes a la laguna, a pesar de la cierta capacidad de depuración de los humedales que le circundan, y también de metales traza por los aportes de residuos mineros (Capítulo 11). De hecho los metales traza están presentes en los sedimentos de la laguna, y su distribución se ha caracterizado en la columna sedimentaria relacionándola con la granulometría y el contenido de materia orgánica del sedimento (Capítulo 12). Posteriormente se describe la entrada de diversos contaminantes orgánicos, incluyendo pesticidas y fármacos a través de la rambla del Albujón, y su distribución estacional en agua y sedimento de la laguna (Capítulo 13). Este segundo bloque finaliza con el Capítulo 14 en el que se describe la bioacumulación de hidrocarburos aromáticos policíclicos, pesticidas y fármacos en moluscos y peces del Mar Menor, así como los efectos biológicos que la carga contaminante que accede a través de la rambla del Albujón produce en los organismos que allí habitan. El libro concluye con un breve epílogo redactado por los editores de este libro.Versión del edito

Integrated Ecological Modeling and Decision Analysis Within the Everglades Landscape

Planning for complex ecosystem restoration projects involves integrating ecological modeling with analysis of performance trade-offs among restoration alternatives. The authors used the Everglades Landscape Model and Multi-Criteria Decision Analysis to explore the effect of simulated ecosystem performance, risk preferences, and criteria weights on the ranking of three alternatives to restoring overland sheet flow in the Everglades. The ecological model outputs included both hydrologic and water quality criteria. Results were scored in the decision analysis framework, highlighting the trade-offs between hydrologic restoration and water quality constraints. Given equal weighting of performance measures, the alternative with more homogenous sheet flow was preferred over other alternatives, despite evidence of some localized eutrophication risk

Shifting Ground: Landscape-Scale Modeling of Biogeochemical Processes under Climate Change in the Florida Everglades

Scenarios modeling can be a useful tool to plan for climate change. In this study, we help Everglades restoration planning to bolster climate change resiliency by simulating plausible ecosystem responses to three climate change scenarios: a Baseline scenario of 2010 climate, and two scenarios that both included 1.5 °C warming and 7% increase in evapotranspiration, and differed only by rainfall: either increase or decrease by 10%. In conjunction with output from a water-use management model, we used these scenarios to drive the Everglades Landscape Model to simulate changes in a suite of parameters that include both hydrologic drivers and changes to soil pattern and process. In this paper we focus on the freshwater wetlands; sea level rise is specifically addressed in prior work. The decreased rainfall scenario produced marked changes across the system in comparison to the Baseline scenario. Most notably, muck fire risk was elevated for 49% of the period of simulation in one of the three indicator regions. Surface water flow velocity slowed drastically across most of the system, which may impair soil processes related to maintaining landscape patterning. Due to lower flow volumes, this scenario produced decreases in parameters related to flow-loading, such as phosphorus accumulation in the soil, and methylmercury production risk. The increased rainfall scenario was hydrologically similar to the Baseline scenario due to existing water management rules. A key change was phosphorus accumulation in the soil, an effect of flow-loading due to higher inflow from water control structures in this scenario

Persistent urinary podocyte loss following preeclampsia may reflect subclinical renal injury.

Studies have shown that podocyturia, i.e., urinary loss of viable podocytes (glomerular epithelial cells), is associated with proteinuria in preeclampsia. We postulated that urinary podocyte loss may persist after preeclamptic pregnancies, thus resulting in renal injury. This may lead to future chronic renal injury. In addition, we compared the postpartum levels of the angiogenic factors, which previously have been associated with preeclampsia, between normotensive versus preeclamptic pregnancies.The diagnosis of preeclampsia was confirmed using standard clinical criteria. Random blood and urine samples were obtained within 24 hours prior to delivery and 5 to 8 weeks postpartum. Urine sediments were cultured for 24 hours to select for viable cells and staining for podocin was used to identify podocytes. Serum samples were analyzed for the levels of angiogenic markers using ELISA (enzyme-linked immunosorbent assay) methodology.At delivery, preeclamptic patients (n = 10) had significantly higher proteinuria (p = 0.006) and podocyturia (p<0.001) than normotensive pregnant patients (n = 18). Postpartum proteinuria was similar between these two groups (p = 0.37), while podocyturia was present in 3 of 10 women with preeclampsia and in none of the normotensive controls (p = 0.037). Angiogenic marker levels, including placental growth factor, soluble vascular endothelial growth factor receptor fms-like tyrosine kinase receptor-1 and endoglin, were not significantly different between women with preeclampsia and women with a normotensive pregnancy, either at delivery or postpartum.Persistent urinary podocyte loss after preeclamptic pregnancies may constitute a marker of ongoing, subclinical renal injury

Visioning the Future: Scenarios Modeling of the Florida Coastal Everglades

In this paper, we provide screening-level analysis of plausible Everglades ecosystem response by 2060 to sea level rise (0.50 m) interacting with macroclimate change (1.5 °C warming, 7% increase in evapotranspiration, and rainfall that either increases or decreases by 10%). We used these climate scenarios as input to the Ecological Landscape Model to simulate changes to seven interactive hydro-ecological metrics. Mangrove forest and other marine influences migrated up to 15 km inland in both scenarios, delineated by the saltwater front. Freshwater habitat area decreased by 25–30% under our two climate change scenarios and was largely replaced by mangroves and, in the increased rainfall scenario, open water as well. Significant mangroves drowned along northern Florida Bay in both climate change scenarios due to sea level rise. Increased rainfall of 10% provided significant benefits to the spatial and temporal salinity regime within the marine-influenced zone, providing a more gradual and natural adjustment for at-risk flora and fauna. However, increased rainfall also increased the risk of open water, due to water depths that inhibited mangrove establishment and reduced peat accumulation rates. We infer that ecological effects related to sea level rise may occur in the extreme front-edge of saltwater intrusion, that topography will control the incursion of this zone as sea level rises, and that differences in freshwater availability will have ecologically significant effects on ecosystem resilience through the temporal and spatial pattern of salinity changes

Subject characteristics according to pregnancy outcome.

<p>T-test for continuous variables, Fisher’s exact test for discrete variables (for those with >2 levels, the lowest was compared to non-lowest as a group).</p

Clinical Parameters and Angiogenic Markers at 2: Delivery and Post-Partum.

a<p>Kruskal Wallis rank sum test.</p>b<p>Fisher’s exact test.</p><p>NOTE: <b>Bold</b> indicates statistical significance, i.e. p≤0.05.</p

Podocyturia assay.

<p>Hoechst nuclear staining (blue); podocin antibody followed by a secondary fluorescein isothiocyanate-labeled antibody (green).</p