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

Image Search Re ranking based on Topic Diversity Using K-NN Algorithm

The developing measure of client labeled sight and sound has driven social picture examination and recovery gain significance which has helped individuals arrange and get to client labeled mixed media. Client labeling is uncontrolled, includes uncertainty and profoundly customized thus a crucial inquiry emerges how to decipher the importance of client contributed tag  concerning the visual substance depicted by the tag. Picture’s significance and decent variety are considered and a social re-ranking framework for tag- based picture recovery. As per individual visual data, semantic data and social pieces of information the pictures are re-positioned. The underlying outcomes incorporate pictures contributed by various social clients. Every client may contribute a few pictures. Consequently, first, these pictures are arranged by between clients re-positioning. The clients that have a higher commitment to the given question are positioned higher. At that point, consecutive checking time stamp positioning is performed in which the ideal yield is acquired on the premise of title data and the ongoing time stamp which improves the decent variety execution of picture positioning framework. It additionally checks a number of perspectives used to enhance the importance execution of the picture recovery results. The last recovered outcomes are made out of the chose pictures. Catchphrase importance coordinates the information is recovered for the social picture dataset to quicken the seeking procedure

IMAGE SEGMENTATION TECHNIQUES IN MEDICAL ANALYSIS “A BOON FOR DETECTION OF CANCER”: A REVIEW

mage processing and computer vision systems can enhance the diagnostic capability of physicians by reducing the time required and resulting in accurate diagnosis. This paper presents the review of resentpublished segmentation and classification techniques for detection of Brain Tumors using Magnetic Resonance Images, which is an open challenge in the field of medical science till date. We present the comparative study of a couple of algorithms based on the technique of segmentation, extraction and classification of the images. Initially we start with segmentation based on localindependent projection-based classification, followed by segmentation using adaptive clustering and Level set method comparing these with the result of computer-aided detection /diagnosis involving the process of pulsed coupled neural network for image segmentation, followed by discrete wavelet transforms for feature extraction and feed forward back propagation neural network for classificatio

Study of Nitrogen Rates and Nano Urea Effects on Physiological Parameters and Yield of Safflower (Carthamus tinctorius L.)

Safflower (Carthamus tinctorius L.) is an important oil seed crop, essential as vegetable oil for humans and feed for livestock. The experiment was conducted in a split plot design to study the effects of foliar application of nano urea and urea on safflower growth and development. The results showed that application of 100% nitrogen in the form of urea topdressing at vegetative stage and foliar spray of nano urea twice at flowering and seed filling stages significantly improved the physiological parameters viz. plant height (cm), primary branches of safflower. The CSI, RWC, Seed yield (kg/ha), 100 seed weight (g) and hull content (%) of safflower also significantly improved with 100% N and foliar spray of nano urea twice at flowering and seed filling stages. The result from the study suggests that application of urea as split doses and foliar spray of nano urea at reproductive stage is beneficial for the crop and will improve seed yield and oil quality of safflower. Foliar application of nano urea improves the nutrient uptake by the crop through its slow and controlled release of nutrients. It also helps in reducing environmental pollution due to leaching of fertilizers

REVIEW PAPER ON EFFECT OF ALUMINIUM DROSS ON PROPERTIES OF CONCRETE

The Bhima River is a main river in South India. It flows southeast for 861 kilometers (535 mi) through Maharashtra, Karnataka, and Telangana states, before inflowing the Krishna River. Along the river stretch there are about 7000 industries comprise Large, middling and little scale units according to CPCB. Most of the industry are located in the Maharashtra Industrial enlargement Corporation (MIDC). The river is 70% polluted by industries pollution and 30% by domestic wastewater. The following decision article presents the termination of the work approved out by the researchers in the past on the various River wate

Prevalence and severity of metabolic acidosis in patients on maintenance hemodialysis in India

Aim: Metabolic acidosis is a feature of chronic kidney disease (CKD) due to the reduced capacity of the kidney to synthesize ammonia and excrete hydrogen ions. Among the many goals of hemodialysis (HD), the role in correction of metabolic acidosis is an important one. To assess the prevalence and severity of metabolic acidosis in the Indian patients of CKD, who are on maintenance HD (MHD). Methods: This is a cross-sectional study on 35 patients conducted at two centers in Western part of India. The demographic, clinical, and laboratory assessments were done on chronic stable patients receiving MHD. The prevalence and severity of metabolic acidosis were evaluated. Results: Metabolic acidosis was found in 22 out of 35 patients (62.85%), with mean predialysis serum pH and HCO3 of 7.32 ± 0.083 and 20.37 ± 4.94 mmol/L, respectively. Conclusion: Metabolic acidosis is significantly prevalent in patients on MHD in India

Discovery of Imidazo[1,2‑<i>a</i>]pyridine Ethers and Squaramides as Selective and Potent Inhibitors of Mycobacterial Adenosine Triphosphate (ATP) Synthesis

The approval of bedaquiline to treat tuberculosis has validated adenosine triphosphate (ATP) synthase as an attractive target to kill Mycobacterium tuberculosis (Mtb). Herein, we report the discovery of two diverse lead series imidazo­[1,2-<i>a</i>]­pyridine ethers (IPE) and squaramides (SQA) as inhibitors of mycobacterial ATP synthesis. Through medicinal chemistry exploration, we established a robust structure–activity relationship of these two scaffolds, resulting in nanomolar potencies in an ATP synthesis inhibition assay. A biochemical deconvolution cascade suggested cytochrome c oxidase as the potential target of IPE class of molecules, whereas characterization of spontaneous resistant mutants of SQAs unambiguously identified ATP synthase as its molecular target. Absence of cross resistance against bedaquiline resistant mutants suggested a different binding site for SQAs on ATP synthase. Furthermore, SQAs were found to be noncytotoxic and demonstrated efficacy in a mouse model of tuberculosis infection

Discovery of Imidazo[1,2‑<i>a</i>]pyridine Ethers and Squaramides as Selective and Potent Inhibitors of Mycobacterial Adenosine Triphosphate (ATP) Synthesis

The approval of bedaquiline to treat tuberculosis has validated adenosine triphosphate (ATP) synthase as an attractive target to kill Mycobacterium tuberculosis (Mtb). Herein, we report the discovery of two diverse lead series imidazo­[1,2-<i>a</i>]­pyridine ethers (IPE) and squaramides (SQA) as inhibitors of mycobacterial ATP synthesis. Through medicinal chemistry exploration, we established a robust structure–activity relationship of these two scaffolds, resulting in nanomolar potencies in an ATP synthesis inhibition assay. A biochemical deconvolution cascade suggested cytochrome c oxidase as the potential target of IPE class of molecules, whereas characterization of spontaneous resistant mutants of SQAs unambiguously identified ATP synthase as its molecular target. Absence of cross resistance against bedaquiline resistant mutants suggested a different binding site for SQAs on ATP synthase. Furthermore, SQAs were found to be noncytotoxic and demonstrated efficacy in a mouse model of tuberculosis infection