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OBJECTIVES To evaluate the diagnostic performance of N-terminal pro-B-type natriuretic peptide (NT-proBNP) thresholds for acute heart failure and to develop and validate a decision support tool that combines NT-proBNP concentrations with clinical characteristics. DESIGN Individual patient level data meta-analysis and modelling study. SETTING Fourteen studies from 13 countries, including randomised controlled trials and prospective observational studies. PARTICIPANTS Individual patient level data for 10 369 patients with suspected acute heart failure were pooled for the meta-analysis to evaluate NT-proBNP thresholds. A decision support tool (Collaboration for the Diagnosis and Evaluation of Heart Failure (CoDE-HF)) that combines NT-proBNP with clinical variables to report the probability of acute heart failure for an individual patient was developed and validated. MAIN OUTCOME MEASURE Adjudicated diagnosis of acute heart failure. RESULTS Overall, 43.9% (4549/10 369) of patients had an adjudicated diagnosis of acute heart failure (73.3% (2286/3119) and 29.0% (1802/6208) in those with and without previous heart failure, respectively). The negative predictive value of the guideline recommended rule-out threshold of 300 pg/mL was 94.6% (95% confidence interval 91.9% to 96.4%); despite use of age specific rule-in thresholds, the positive predictive value varied at 61.0% (55.3% to 66.4%), 73.5% (62.3% to 82.3%), and 80.2% (70.9% to 87.1%), in patients aged 75 years, respectively. Performance varied in most subgroups, particularly patients with obesity, renal impairment, or previous heart failure. CoDE-HF was well calibrated, with excellent discrimination in patients with and without previous heart failure (area under the receiver operator curve 0.846 (0.830 to 0.862) and 0.925 (0.919 to 0.932) and Brier scores of 0.130 and 0.099, respectively). In patients without previous heart failure, the diagnostic performance was consistent across all subgroups, with 40.3% (2502/6208) identified at low probability (negative predictive value of 98.6%, 97.8% to 99.1%) and 28.0% (1737/6208) at high probability (positive predictive value of 75.0%, 65.7% to 82.5%) of having acute heart failure. CONCLUSIONS In an international, collaborative evaluation of the diagnostic performance of NT-proBNP, guideline recommended thresholds to diagnose acute heart failure varied substantially in important patient subgroups. The CoDE-HF decision support tool incorporating NT-proBNP as a continuous measure and other clinical variables provides a more consistent, accurate, and individualised approach. STUDY REGISTRATION PROSPERO CRD42019159407.

Background & AimsLiver cirrhosis is a major cause of death worldwide, and its prevalence is growing rapidly due to the growth of obesity and diabetes population with non-alcoholic fatty liver disease (NAFLD). Yet, no effective therapeutics have been developed to treat NAFLD or its more advanced stage, non-alcoholic steatohepatitis (NASH). This has raised great concern for a representative liver model to be developed so that novel drugs could be screened, identified and developed. Presently, we aim to develop a liver organoid entirely from human induced pluripotent stem cells (hiPSC) to model liver fibrogenesis and NAFLD.MethodsHepatoblasts (HBs), mesenchymal stem cells (MSCs), hepatic stellate cell (HSCs) and endothelial cells (ECs) were derived from hiPSCs, allowed to self-organized and differentiated into liver organoids. Liver functions, transcriptomic and protein expression of liver organoids were characterized and validated. Liver organoids were exposed to thioacetamide (TAA) and free fatty acids (FFA) to be induced into liver disease model.ResultsThe liver organoids we fabricated were highly vascularized, exhibited liver-specific functions and hepatic cellular spatial organization. The presence of liver specific ECs, macrophages and cholangiocytes were found within our organoids. TAA induced fibrosis in our liver organoids that exhibited diminished liver functions, elevated pro-inflammatory cytokines and fibrosis-related gene expression, as well as extensive collagen deposit. Organoids treated with FFA developed steatosis, inflammation and fibrosis.ConclusionsWe generated a novel method, that is Matrigel-independent and size-controllable, for making human liver organoids. These organoids can potentially be utilized as tissue-mimetic in vitro model for high throughput screening to identify drugs that can be used to treat liver fibrosis and NAFLD.

Most phenotype-identification methods in cell-based screening assume prior knowledge about expected phenotypes or involve intricate parameter-setting. They are useful for analysis targeting known phenotype properties; but need exists to explore, with minimum presumptions, the potentially-interesting phenotypes derivable from data. We present a method for this exploration, using clustering to eliminate phenotype-labelling requirement and GUI visualisation to facilitate parameter-setting. The steps are: outlier-removal, cell clustering and interactive visualisation for phenotypes refinement. For drug-siRNA study, we introduce an auto-merging procedure to reduce phenotype redundancy. We validated the method on two Golgi apparatus screens and showcase its contribution for better understanding of screening-images. Copyright © 2011 Inderscience Enterprises Ltd.

An in vitro study was undertaken to evaluate the compatibility of indigenous plant growth promoting rhizobacteria (PGPR) with commonly used inorganic and organic sources of fertilizers in tea plantations. The nitrogenous, phosphatic and potash fertilizers used for this study were urea, rock phosphate and muriate of potash, respectively. The organic sources of fertilizers neem cake, composted coir pith and vermicompost were also used. PGPRs such as nitrogen fixer; Azospirillum lipoferum, Phosphate Solubilizing Bacteria (PSB); Pseudomonas putida, Potassium Solubilizing Bacteria (KSB); Burkholderia cepacia and Pseudomonas putida were used for compatibility study. Results were indicated that PGPRs preferred the coir pith and they proved their higher colony establishment in the formulation except Azospirillum spp. that preferred vermicompost for their establishment. The optimum dose of neem cake powder …

THE outbreak of human pandemic influenza (H1N1) 2009 (pH1N1) that was first recorded in Mexico and then the USA in April 2009 spread to a number of countries in Europe and Asia (World Health Organization [WHO] 2009). The aetiological agent of pH1N1 is a reassortant virus that contains six gene segments from a North American triple-reassortant swine H1-subtype virus and the neuraminidase (NA) and matrix (M) genes from a Eurasian lineage H1N1 swine influenza. This latter virus existed in pigs around 10 to 20 years ago, as determined by Bayesian molecular clock analysis (Garten and others 2009, Smith and others 2009). More recently, commercial pigs in Canada, Argentina, Australia, Singapore, Norway, the USA, Italy, Germany and the UK have been confirmed to be infected with the pH1N1 virus, suggesting efficient transmission between human beings as well as within pig populations (International Society for Infectious Diseases 2009). Pigs infected either artificially or naturally with pH1N1 show similar clinical signs to those of pigs infected with swine influenza A virus (SIV). Clinical signs vary from mild (characterised by depression, fever, sneezing and nasal discharge) to inapparent (Hofshagen and others 2009, Howden and others 2009, Brookes and others 2010, Pasma and Joseph 2010, Weingartl and others 2010, Welsh and others 2010). Reports suggest that in most of these cases, pH1N1-infected human beings transmitted the virus to pigs; however, in some cases in Canada, pigs were suspected to have infected other pigs directly (International Society for Infectious Diseases 2009, Pasma and Joseph 2010). Before the emergence of pH1N1 in South Korea, H1N1, H1N2 and H3N2 SIVs were the principal viruses isolated from pig populations (Lee and others 2008). However, due to its low mortality and economic impact, swine influenza was not designated as a nationally …