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

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of &lt;15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P&lt;0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P&lt;0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Mayaro virus pathogenesis and immunity in rhesus macaques.

Mayaro virus (MAYV) is a mosquito-transmitted alphavirus that causes debilitating and persistent arthritogenic disease. While MAYV was previously reported to infect non-human primates (NHP), characterization of MAYV pathogenesis is currently lacking. Therefore, in this study we characterized MAYV infection and immunity in rhesus macaques. To inform the selection of a viral strain for NHP experiments, we evaluated five MAYV strains in C57BL/6 mice and showed that MAYV strain BeAr505411 induced robust tissue dissemination and disease. Three male rhesus macaques were subcutaneously challenged with 105 plaque-forming units of this strain into the arms. Peak plasma viremia occurred at 2 days post-infection (dpi). NHPs were taken to necropsy at 10 dpi to assess viral dissemination, which included the muscles and joints, lymphoid tissues, major organs, male reproductive tissues, as well as peripheral and central nervous system tissues. Histological examination demonstrated that MAYV infection was associated with appendicular joint and muscle inflammation as well as presence of perivascular inflammation in a wide variety of tissues. One animal developed a maculopapular rash and two NHP had viral RNA detected in upper torso skin samples, which was associated with the presence of perivascular and perifollicular lymphocytic aggregation. Analysis of longitudinal peripheral blood samples indicated a robust innate and adaptive immune activation, including the presence of anti-MAYV neutralizing antibodies with activity against related Una virus and chikungunya virus. Inflammatory cytokines and monocyte activation also peaked coincident with viremia, which was well supported by our transcriptomic analysis highlighting enrichment of interferon signaling and other antiviral processes at 2 days post MAYV infection. The rhesus macaque model of MAYV infection recapitulates many of the aspects of human infection and is poised to facilitate the evaluation of novel therapies and vaccines targeting this re-emerging virus

The SuperCam Remote Sensing Suite for MARS 2020: Nested and Co-Aligned LIBS, Raman, and VISIR Spectroscopies, and color micro-imaging

As chartered by the Science Definition Team, the Mars 2020 mission addresses four primary objectives: A. Characterize the processes that formed and modified the geologic record within an astrobiologically relevant ancient environment, B. Perform astrobiologically relevant investigations to determine habitability, search for materials with biosignature presentation potential, and search for evidence of past life, C. Assemble a returnable cache of samples and D. Contribute to preparation for human exploration of Mars. The SuperCam instrument, selected for the Mars 2020 rover, as a suite of four instruments, provides nested and co-aligned remote investigations: Laser Induced Breakdown Spectroscopy (LIBS), Raman spectroscopy and time-resolved fluorescence (TRF), visible and near-infrared spectroscopy (VISIR), and high resolution color imaging (RMI). SuperCam appeals broadly to the four Mars 2020 objectives.In detail, SuperCam will perform:1. Microscale mineral identification by combining LIBS elemental and VISIR mineralogical spectroscopies, especially targeting secondary minerals2. Determine the sedimental stratigraphy through color imaging and LIBS and VISIR spectroscopy3. Search for organics and bio-signatures with LIBS and Raman spectroscopy4. Quantify the volatile content of the rocks by LIBS spectroscopy to determine the degree of aquaeous alteration5. Characterize the texture of the rocks by color imaging to determine their alteration processes6. Characterize the rocks' coatings by LIBS spectroscopy7. Characterize the soil and its potential for biosignature preservation8. Monitor the odd-oxygen atmospheric chemistry.To meet these goals SuperCam will perform LIBS spectroscopy on 0.5 mm spot up to 7-meter distance, perform Raman and time-resolved fluoresence up to 12-m distance with a 0.8 mrad angular resolution, a 100 ns time gating in the 534-850 nm spectral range, acquire VISIR spectra in the range 0.4-0.85 μm with a resolution of 0.35 nm, and in the IR range over 1.3-2.6 μm, rich in mineral signatures, with a resolution of 20 nm, and provide RGB images with an angular resolution of 40 μrad over a FOV of 20 mrad.We will present the science performances of SuperCam and the forecasted operation plans

Jezero Crater Floor and Delta Chemistry and Mineralogy Observed by SuperCam in the First 1.5 Years of the Perseverance Rover Mission

International audienceJezero crater was chosen for exploration and sample collection by Perseverance due to its history as a lake with river deltas, its diverse mineralogy, including carbonates observed from orbit, and as a potential site to calibrate crater counting ages with radiometric dates of samples to be returned to Earth. This presentation focuses on the results of SuperCam, which uses LIBS for remote elemental chemistry, VISIR and remote Raman spectroscopy for mineral compositions and alteration, includes a microphone, and performs high-resolution imaging for textures and morphology. In the first year after landing, SuperCam and other instruments were used to explore Jezero’s floor. We found that all of the floor units are igneous, with lava flows comprising the upper units as part of the Máaz formation, while the lower formation, Séítah, is an olivine cumulate, produced by gravitational settling of olivine crystals in a large melt body. Artuby ridge, just outside the SW portion of Séítah and stratigraphically just above it, contains up to 60% pyroxene. The upper portions of the Máaz formation are more enriched in plagioclase, with the uppermost Ch’al member having the most evolved composition, along with the Content member, pitted rocks directly overlying the main cumulate portion of Séítah. After exploring the floor, Perseverance drove to the delta formation and began a walk-about style of observations starting at Enchanted Lake, just below an arm of the delta formation, and then moving into Hawksbill Gap, climbing 18 m in elevation between Devil’s Tanyard, Sunset Hill, and Hogwallow flats. Delta compositions initially displayed higher phyllosilicate contents, identified by absorptions at 1.4, 1.9, and 2.3 µm, and by higher LIBS H peak areas. Farther up, compositions changed to sulfur-bearing in lower locations within the continuous fine-grained light-toned strata (e.g., Pignut Mountain, Sol 463) and carbonate-rich in upper strata. Veins were observed, consisting of Mg-Fe carbonate (Elder Ridge, Sol 459) and anhydrite (Reid’s Gap, Sol 466). The sulfates suggest precipitation of these salts at a later stage, as the lake was evaporating. Carbonates and sulfates in veins in different locations indicate that groundwater was active in the lithified sediments and had significantly different chemistry at different intervals

Jezero Crater Floor and Delta Chemistry and Mineralogy Observed by SuperCam in the First 1.5 Years of the Perseverance Rover Mission

International audienceJezero crater was chosen for exploration and sample collection by Perseverance due to its history as a lake with river deltas, its diverse mineralogy, including carbonates observed from orbit, and as a potential site to calibrate crater counting ages with radiometric dates of samples to be returned to Earth. This presentation focuses on the results of SuperCam, which uses LIBS for remote elemental chemistry, VISIR and remote Raman spectroscopy for mineral compositions and alteration, includes a microphone, and performs high-resolution imaging for textures and morphology. In the first year after landing, SuperCam and other instruments were used to explore Jezero’s floor. We found that all of the floor units are igneous, with lava flows comprising the upper units as part of the Máaz formation, while the lower formation, Séítah, is an olivine cumulate, produced by gravitational settling of olivine crystals in a large melt body. Artuby ridge, just outside the SW portion of Séítah and stratigraphically just above it, contains up to 60% pyroxene. The upper portions of the Máaz formation are more enriched in plagioclase, with the uppermost Ch’al member having the most evolved composition, along with the Content member, pitted rocks directly overlying the main cumulate portion of Séítah. After exploring the floor, Perseverance drove to the delta formation and began a walk-about style of observations starting at Enchanted Lake, just below an arm of the delta formation, and then moving into Hawksbill Gap, climbing 18 m in elevation between Devil’s Tanyard, Sunset Hill, and Hogwallow flats. Delta compositions initially displayed higher phyllosilicate contents, identified by absorptions at 1.4, 1.9, and 2.3 µm, and by higher LIBS H peak areas. Farther up, compositions changed to sulfur-bearing in lower locations within the continuous fine-grained light-toned strata (e.g., Pignut Mountain, Sol 463) and carbonate-rich in upper strata. Veins were observed, consisting of Mg-Fe carbonate (Elder Ridge, Sol 459) and anhydrite (Reid’s Gap, Sol 466). The sulfates suggest precipitation of these salts at a later stage, as the lake was evaporating. Carbonates and sulfates in veins in different locations indicate that groundwater was active in the lithified sediments and had significantly different chemistry at different intervals