Canagliflozin and Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus and Chronic Kidney Disease in Primary and Secondary Cardiovascular Prevention Groups

Background: Canagliflozin reduces the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, but effects on specific cardiovascular outcomes are uncertain, as are effects in people without previous cardiovascular disease (primary prevention). Methods: In CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation), 4401 participants with type 2 diabetes mellitus and chronic kidney disease were randomly assigned to canagliflozin or placebo on a background of optimized standard of care. Results: Primary prevention participants (n=2181, 49.6%) were younger (61 versus 65 years), were more often female (37% versus 31%), and had shorter duration of diabetes mellitus (15 years versus 16 years) compared with secondary prevention participants (n=2220, 50.4%). Canagliflozin reduced the risk of major cardiovascular events overall (hazard ratio [HR], 0.80 [95% CI, 0.67-0.95]; P=0.01), with consistent reductions in both the primary (HR, 0.68 [95% CI, 0.49-0.94]) and secondary (HR, 0.85 [95% CI, 0.69-1.06]) prevention groups (P for interaction=0.25). Effects were also similar for the components of the composite including cardiovascular death (HR, 0.78 [95% CI, 0.61-1.00]), nonfatal myocardial infarction (HR, 0.81 [95% CI, 0.59-1.10]), and nonfatal stroke (HR, 0.80 [95% CI, 0.56-1.15]). The risk of the primary composite renal outcome and the composite of cardiovascular death or hospitalization for heart failure were also consistently reduced in both the primary and secondary prevention groups (P for interaction >0.5 for each outcome). Conclusions: Canagliflozin significantly reduced major cardiovascular events and kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, including in participants who did not have previous cardiovascular disease

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

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 <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >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 <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<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<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

Burned Region Analysis using Normalized Burn Ratio Index (NBRI) in 2019 Forest Fires in Indonesia (Case study : Pinggir-Mandau District, Bengkalis, Riau)

Forest fire is a hazard that common to happen in Indonesia every year, whether from natural or human-induced factor. These fires can be uncontrollable and destruct the forest. Furthermore, these can affect the health of the people, the biodiversity, the disruption in transportation and the socioeconomic of the affected region. The total area calculated was burned is 875.756 hectares in the entire country in 2019, the biggest lost after 2015. Thus, the study conducted in some affected area in Riau Province, Sumatra, Indonesia where consistently suffered from the fire by remote sensing and GIS approach. The study of the burned area was investigated using a formulated index called NBRI (Normalized Burn Ratio Index) based on Near Infrared (NIR) and Shortwave Infrared (SWIR) spectral reflectance of Landsat 8 OLI/TIRS Satellite Imageries. The two values of NBRI from post and pre-fire images were calculated to define differenced NBR (dNBR) to assess its severity. It is found that about 4,7 %, or about 11.014 hectares of the area of the study which was about 234.864 hectares was burned. 90,3 % of the burned area was located in the vegetated area, especially forest area with 50,25 % of those cover the burned area. The validation was using visual interpretation based on SPOT 7 pansharpened images resulted in acceptable agreement with kappa coefficient value of 0,83. The information on the maps can be used to develop rehabilitation planning or predict the area for potential fire hazard in the future

Equilibrium concentration of singlet oxygen in photoreaction of reaction center/carbon nanotube bionanocomposites

The reaction center protein is the unit in the photosynthetic organisms in which the primary events of the photoelectric energy conversion take place during photosynthesis. When the photochemistry following the excitation of the reaction center by light is oversaturated there is a large probability to form reactive oxygen species (ROS, e.g., singlet oxygen (O-1(2))). Because the ROS components decrease the overall yield of the photochemical energy conversion there is a considerable effort in many laboratories to find conditions to reduce these harmful compounds. The aim of our work is to create a system by using carbon nanotubes (CNTs) and RCs for efficient light-energy conversion. The role of the O-1(2) that destroys the RC structure is discussed. 1,3-Diphenylisobenzofuran was used to detect the concentration of the O-1(2). Although, O-1(2) can be sensitized by CNTs in certain conditions, in our experiments the main sources of the O-1(2) are the RCs. The concentration of the O-1(2) in the equilibrium is determined by the forward sensitization and the backward deactivation processes of the components and functions of the CNT/RC composite. (C) 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinhei

Crop Type Classification by DESIS Hyperspectral Imagery and Machine Learning Algorithms

Developments in space-based hyperspectral sensors, advanced remote sensing, and machine learning can help crop yield measurement, modelling, prediction, and crop monitoring for loss prevention and global food security. However, precise and continuous spectral signatures, important for large-area crop growth monitoring and early prediction of yield production with cutting-edge algorithms, can be only provided via hyperspectral imaging. Therefore, this article used new-generation Deutsches Zentrum für Luft- und Raumfahrt Earth Sensing Imaging Spectrometer (DESIS) images to classify the main crop types (hybrid corn, soybean, sunflower, and winter wheat) in Mezőhegyes (southeastern Hungary). A Wavelet-attention convolutional neural network (WA-CNN), random forest and support vector machine (SVM) algorithms were utilized to automatically map the crops over the agricultural lands. The best accuracy was achieved with the WA-CNN, a feature-based deep learning algorithm and a combination of two images with overall accuracy (OA) value of 97.89% and the user's accuracy producer's accuracy was from 97% to 99%. To obtain this, first, factor analysis was introduced to decrease the size of the hyperspectral image data cube. A wavelet transform was applied to extract important features and combined with the spectral attention mechanism CNN to gain higher accuracy in mapping crop types. Followed by SVM algorithm reported OA of 87.79%, with the producer's and user's accuracies of its classes ranging from 79.62% to 96.48% and from 79.63% to 95.73%, respectively. These results demonstrate the potentiality of DESIS data to observe the growth of different crop types and predict the harvest volume, which is crucial for farmers, smallholders, and decision-makers