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

Vivre aux confins de Central Park et de Harlem à New York. Trajets, regards et formes urbaines

Am Rand von Central Park und Harlem in New York Der physische Verfall verstärkt das Gefühl der Bedrohung bei dem auswärtigen Besucher, der in New York die Straßen Harlems durchstreift. Die soziale Forderung nach stärkerer Polizeikontrolle blendet den der ungleichen Behandlung der Räume zugrunde liegenden wirtschaftlichen und gesellschaftlichen Konflikt aus. Die Fokali-sierung der Ängste auf den Andersartigen bedroht die Nutzung gemeinsamer Orte, etwa der Spielplätze.Living at the fringes of Central Park and Harlem in New York Physical degradation increases the impression of risk for the newly-arrived city-dweller on the streets of Harlem in New York. Social demand for reinforced policing masks the economic and social conflict at the origin of unequal spatial treatment. The embodiment of fear in other people is undermining the enjoyment of public places such as playgrounds.La dégradation physique accroît le sentiment de risque chez le citadin venu d'ailleurs qui parcourt les rues de Harlem à New York. La demande sociale de renforcement du contrôle policier occulte le conflit économique et social à l'origine du traitement inégal des espaces. La focalisation de la peur sur l'autre menace la jouissance de lieux communs comme les aires de jeux.Vivir en los confines Central Park y Harlem en Nueva York La degradación física aumenta el sentimiento de riesgo en el habitante de otras partes de la ciudad que recorre las calles de Harlem. La demanda social de refuerzo del control policial oculta el conflicto social que da origen al tratamiento desigual de los espacios. La focalización del miedo en el otro pone en peligro la posibilidad de disfrutar de los lugares comunes como de las áreas de juego.Nevarez Julia, Maury Hervé. Vivre aux confins de Central Park et de Harlem à New York. Trajets, regards et formes urbaines. In: Les Annales de la recherche urbaine, N°83-84, 1999. Au risque des espaces publics. pp. 148-154

Predicción del éxito de proyectos de videojuegos en Kickstarter con aprendizaje automático

Kickstarter se ha convertido en el principal medio de financiamiento para proyectos de desarrolladores independientes. En esta plataforma se han subvencionado exitosamente alrededor de 2,500 proyectos de videojuegos. Aún cuando la de campañas exitosas parece considerable, es pertinente mencionar que 12,500 campañas de esta misma categoría fracasaron en recaudar su meta. Kickstarter establece en sus políticas que el capital recaudado en una campa˜na debe ser devuelto a sus respectivos contribuyentes, repercutiendo negativamente a los desarrolladores. Por lo tanto, resulta importante encontrar un medio de predección del éxito/fracaso de las campañas de videojuegos. Utilizando una base de datos con datos con variables homologadas de diversas fuentes como Kaggle, Kickstarter, Facebook y otras redes sociales, en el presente artículo se propone el uso de técnicas de desabalance de clases y la regresión logística para la predicción del éxito/fracaso de las campañas. Los resultados experimentales mostraron que es posible predecir el éxito/fracaso de una campa˜na con una media geométrica de 0.8870

Survey of ophthalmic anterior segment findings and intraocular pressure in 95 North American box turtles (Terrapene spp.)

OBJECTIVE: To describe the ophthalmic biomicroscopy findings and intraocular pressures (IOP) in a captive population of box turtles and to determine whether a relationship exists between body morphometrics or health status and IOP. PROCEDURES: Hundred and three box turtles (69 Gulf coast, 24 three-toed, one ornate, one eastern, and eight unidentified) were triaged into three different color-coded groups: green (healthy), yellow (abnormal physical examination with no need for immediate care), and red (immediate care required). Both eyes were evaluated by rebound tonometry and slit-lamp biomicroscopy. Body weight and morphometric data were recorded. RESULTS: Intraocular pressures measurements were available for 190 eyes, slit-lamp biomicroscopy was available for 170 eyes, and morphometric data were available for 81 turtles. IOP in Gulf coast turtles (138 eyes) was 6.7 ± 1.4 mmHg OU. IOP in three-toed turtles (48 eyes) was 8.3 ± 1.5 mmHg OU, which was significantly higher than in Gulf coast turtles (P \u3c 0.0001). No significant IOP differences were noted between genders in both subspecies (P = 0.768). There was a correlation between IOP and health status in three-toed turtles only. There was a mild negative correlation between morphometrics and IOP in Gulf coast and three-toed turtles. Fifteen of 87 turtles had unilateral corneal or lenticular opacities; 3/87 had bilateral corneal or lenticular disease; and 3/87 had adnexal abnormalities. CONCLUSIONS: Different subspecies of box turtles have different normal intraocular pressures as measured by rebound tonometry, which was influenced by the animals\u27 health status in one subspecies. Some morphometric parameters were found to be associated with IOP. Box turtles are often affected with ophthalmic abnormalities of unknown clinical significance

Research in the globalscape : conceptual tools for understanding sites

[[WORKSHOP Within EDRA 35, 2004: Design With Spirit Moderated by Julia Nevarez with contributions from Denise Alcantara, Clio Capitanachi, Jeffrey Pall Wandersman, Suzanne Scheld, Bob Bechtel, Constatine Kijanenko, Dana Taplin, Robert Marans, Ashraf M. Salama, Michael Mitrany, and Sanjoy Mazundar]] Purposes and objectives: While previous workshops have deal with urban research methodologies, this workshop will help uncover those conceptual tools used in the study of environments. While the epistemological foundations of research include a consideration for the origins, methods and limits of knowledge, this workshop will focus on the methods and discuss concepts and spatial metaphors used to speak of the city. Explicitly and implicitly conceptual tools, such as spatial metaphors help to advance the analysis of urban phenomena. Little explanation is given to the underlying conceptual and spatial metaphors of urban though. This workshop will attempt at uncovering the epistemologies produced by the craft of research in the global context by 1) presenting research in specific sites, 2) identifying and describing the spatial metaphors used in the analysis of cities and other settled areas, and 3) examining the discourses these spatial metaphors represent. Expected outcomes: This workshop seeks to offer a platform where to discuss the conceptual tools used in urban research, specifically spatial metaphors that help the analysis of the city and other settled areas. The workshop also seeks to identify the discourses from which these spatial metaphors emerge as a way to advance our awareness of how knowledge is obtained through research. An identification of concepts and spatial metaphors will help identify the possible benefits and limitations of using such conceptual and analytical tools in the production of knowledge about the urban environment. Plans to involve the audience:A reference list and selection of readings will be distributed to participants. There will be three presentations by workshop members that will provide examples of conceptual tools used in the analysis o furban research. A group exercise will help participants in different subgroups identify other conceptual tools that they use in their current research. An open group discussion about the sub-group activities will follow.List of possible participants: Denise Alcantara, Clio Capitanachi, Jeffrey Pall Wandersman, Suzanne Scheld, Bob Bechtel, Constatine Kijanenko, Dana Taplin, Robert Marans, Ashraf M. Salama, Michael Mitrany, and Sanjoy Mazundar

Risk of COVID-19 after natural infection or vaccinationResearch in context

Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health

Risk of COVID-19 after natural infection or vaccinationResearch in context

Summary: Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health

Evolocumab and clinical outcomes in patients with cardiovascular disease

BACKGROUND Evolocumab is a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and lowers low-density lipoprotein (LDL) cholesterol levels by approximately 60%. Whether it prevents cardiovascular events is uncertain. METHODS We conducted a randomized, double-blind, placebo-controlled trial involving 27,564 patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of 70 mg per deciliter (1.8 mmol per liter) or higher who were receiving statin therapy. Patients were randomly assigned to receive evolocumab (either 140 mg every 2 weeks or 420 mg monthly) or matching placebo as subcutaneous injections. The primary efficacy end point was the composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. The key secondary efficacy end point was the composite of cardiovascular death, myocardial infarction, or stroke. The median duration of follow-up was 2.2 years. RESULTS At 48 weeks, the least-squares mean percentage reduction in LDL cholesterol levels with evolocumab, as compared with placebo, was 59%, from a median baseline value of 92 mg per deciliter (2.4 mmol per liter) to 30 mg per deciliter (0.78 mmol per liter) (P<0.001). Relative to placebo, evolocumab treatment significantly reduced the risk of the primary end point (1344 patients [9.8%] vs. 1563 patients [11.3%]; hazard ratio, 0.85; 95% confidence interval [CI], 0.79 to 0.92; P<0.001) and the key secondary end point (816 [5.9%] vs. 1013 [7.4%]; hazard ratio, 0.80; 95% CI, 0.73 to 0.88; P<0.001). The results were consistent across key subgroups, including the subgroup of patients in the lowest quartile for baseline LDL cholesterol levels (median, 74 mg per deciliter [1.9 mmol per liter]). There was no significant difference between the study groups with regard to adverse events (including new-onset diabetes and neurocognitive events), with the exception of injection-site reactions, which were more common with evolocumab (2.1% vs. 1.6%). CONCLUSIONS In our trial, inhibition of PCSK9 with evolocumab on a background of statin therapy lowered LDL cholesterol levels to a median of 30 mg per deciliter (0.78 mmol per liter) and reduced the risk of cardiovascular events. These findings show that patients with atherosclerotic cardiovascular disease benefit from lowering of LDL cholesterol levels below current targets