The utility of B-type natriuretic peptide in predicting postoperative cardiac events and mortality in patients undergoing major emergency non-cardiac surgery

B-type natriuretic peptide (BNP) levels predict cardiovascular risk in several settings. We hypothesized that they would identify individuals at increased risk of complications and mortality following major emergency non-cardiac surgery.Forty patients were studied with a primary end-point of a new post-operative cardiac event, and/or development of significant ECG changes, and/or cardiac death. The main secondary outcome was all cause mortality at 6 months. Preoperative BNP levels were higher in 11 patients who suffered a new postoperative cardiac event (p=0.001) and predicted this outcome with an area under the receiver operating characteristic curve of 0.85 (CI=0.72-0.98,p=0.001). A pre-operative BNP value >170pg.ml-1 has a sensitivity of 82% and a specificity of 79% for the primary end-point. In this small study, pre-operative BNP levels identify patients undergoing major emergency non-cardiac surgery who are at increased risk of early post-operative cardiac events. Larger studies are required to confirm these data.Peer reviewedPreprin

Non-intrusive speech quality prediction using modulation energies and LSTM-network

Many signal processing algorithms have been proposed to improve the quality of speech recorded in the presence of noise and reverberation. Perceptual measures, i.e., listening tests, are usually considered the most reliable way to evaluate the quality of speech processed by such algorithms but are costly and time-consuming. Consequently, speech enhancement algorithms are often evaluated using signal-based measures, which can be either intrusive or non-intrusive. As the computation of intrusive measures requires a reference signal, only non-intrusive measures can be used in applications for which the clean speech signal is not available. However, many existing non-intrusive measures correlate poorly with the perceived speech quality, particularly when applied over a wide range of algorithms or acoustic conditions. In this paper, we propose a novel non-intrusive measure of the quality of processed speech that combines modulation energy features and a recurrent neural network using long short-term memory cells. We collected a dataset of perceptually evaluated signals representing several acoustic conditions and algorithms and used this dataset to train and evaluate the proposed measure. Results show that the proposed measure yields higher correlation with perceptual speech quality than that of benchmark intrusive and non-intrusive measures when considering various categories of algorithms. Although the proposed measure is sensitive to mismatch between training and testing, results show that it is a useful approach to evaluate specific algorithms over a wide range of acoustic conditions and may, thus, become particularly useful for real-time selection of speech enhancement algorithm settings

Technical improvement of the Detia Degesch Phosphine Tolerance Test Kit: Presentation

Phosphine is the most important commonly used fumigant for the control of stored product insects in warehouses and processing facilities globally. However, the improper and extensive use has led to reduced susceptibility to phosphine for several insect species and strains in many parts of the world. To evaluate and quantify this phenomenon, Detia Degesch developed the Detia Degesch Phosphine Tolerance Test Kit (DDPTTK) more than 10 years ago. The use of DDPTTK is based on the exposure of the insects on a high concentration of phosphine (e.g. 3000 ppm) for short exposure periods (e.g. 8-15 min). This kit can be used on site by the fumigation and food industry, and can provide immediate results on the tolerance status of the insect strains that are to be treated. So far, the instructions of DDPTTK refer only to a six insect species. In this work, data for the expansion of knowledge about other species is provided, in order to broaden the spectrum of cases where the kit can be used. Moreover, certain improvements for the use of the kit are introduced, i.e. practical recommendations on the procedure and safety instructions.Phosphine is the most important commonly used fumigant for the control of stored product insects in warehouses and processing facilities globally. However, the improper and extensive use has led to reduced susceptibility to phosphine for several insect species and strains in many parts of the world. To evaluate and quantify this phenomenon, Detia Degesch developed the Detia Degesch Phosphine Tolerance Test Kit (DDPTTK) more than 10 years ago. The use of DDPTTK is based on the exposure of the insects on a high concentration of phosphine (e.g. 3000 ppm) for short exposure periods (e.g. 8-15 min). This kit can be used on site by the fumigation and food industry, and can provide immediate results on the tolerance status of the insect strains that are to be treated. So far, the instructions of DDPTTK refer only to a six insect species. In this work, data for the expansion of knowledge about other species is provided, in order to broaden the spectrum of cases where the kit can be used. Moreover, certain improvements for the use of the kit are introduced, i.e. practical recommendations on the procedure and safety instructions

Differential nuclear scaffold/matrix attachment marks expressed genes†

It is well established that nuclear architecture plays a key role in poising regions of the genome for transcription. This may be achieved using scaffold/matrix attachment regions (S/MARs) that establish loop domains. However, the relationship between changes in the physical structure of the genome as mediated by attachment to the nuclear scaffold/matrix and gene expression is not clearly understood. To define the role of S/MARs in organizing our genome and to resolve the often contradictory loci-specific studies, we have surveyed the S/MARs in HeLa S3 cells on human chromosomes 14–18 by array comparative genomic hybridization. Comparison of LIS (lithium 3,5-diiodosalicylate) extraction to identify SARs and 2 m NaCl extraction to identify MARs revealed that approximately one-half of the sites were in common. The results presented in this study suggest that SARs 5′ of a gene are associated with transcript presence whereas MARs contained within a gene are associated with silenced genes. The varied functions of the S/MARs as revealed by the different extraction methods highlights their unique functional contribution

Depletion of Macrophages Improves Therapeutic Response to Gemcitabine in Murine Pancreas Cancer.

BACKGROUND: The tumor microenvironment (TME) is composed of fibro-inflammatory cells and extracellular matrix (ECM) components. However, the exact contribution of the various TME compartments towards therapeutic response is unknown. Here, we aim to dissect the specific contribution of tumor-associated macrophages (TAMs) towards drug delivery and response in pancreatic ductal adenocarcinoma (PDAC). METHODS: The effect of gemcitabine was assessed in human and murine macrophages, human pancreatic stellate cells (hPSCs), and tumor cells (L3.6pl, BxPC3 and KPC) in vitro. The drug metabolism of gemcitabine was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Preclinical studies were conducted using KrasG12D;p48-Cre and KrasG12D;p53172H;Pdx-Cre mice to investigate gemcitabine delivery at different stages of tumor progression and upon pharmacological TAM depletion. RESULTS: Gemcitabine accumulation was significantly increased in murine PDAC tissue compared to pancreatic intraepithelial neoplasia (PanIN) lesions and healthy control pancreas tissue. In vitro, macrophages accumulated and rapidly metabolized gemcitabine resulting in a significant drug scavenging effect for gemcitabine. Finally, pharmacological TAM depletion enhanced therapeutic response to gemcitabine in tumor-bearing KPC mice. CONCLUSION: Macrophages rapidly metabolize gemcitabine in vitro, and pharmacological depletion improves the therapeutic response to gemcitabine in vivo. Our study supports the notion that TAMs might be a promising therapeutic target in PDAC

GDF15 is an exercise-induced hepatokine regulated by glucagon and insulin in humans

ObjectiveGrowth differentiation factor (GDF)-15 is implicated in regulation of metabolism and circulating GDF15 increases in response to exercise. The source and regulation of the exercise-induced increase in GDF15 is, however not known.MethodPlasma GDF15 was measured by ELISA under the following conditions: 1) Arterial-to-hepatic venous differences sampled before, during, and after exercise in healthy male subjects (n=10); 2) exogenous glucagon infusion compared to saline infusion in resting healthy subjects (n=10); 3) an acute exercise bout with and without a pancreatic clamp (n=6); 4) healthy subjects for 36 hours (n=17), and 5) patients with anorexia nervosa (n=25) were compared to healthy age-matched subjects (n=25). Tissue GDF15 mRNA content was determined in mice in response to exhaustive exercise (n=16).ResultsThe splanchnic bed released GDF15 to the circulation during exercise and increasing the glucagon-to-insulin ratio in resting humans led to a 2.7-fold (P<0.05) increase in circulating GDF15. Conversely, inhibiting the exercise-induced increase in the glucagon-to-insulin ratio blunted the exercise-induced increase in circulating GDF15. Fasting for 36 hours did not affect circulating GDF15, whereas resting patients with anorexia nervosa displayed elevated plasma concentrations (1.4-fold, P<0.05) compared to controls. In mice, exercise increased GDF15 mRNA contents in liver, muscle, and adipose tissue.ConclusionIn humans, GDF15 is a “hepatokine” which increases during exercise and is at least in part regulated by the glucagon-to-insulin ratio. Moreover, chronic energy deprivation is associated with elevated plasma GDF15, which supports that GDF15 is implicated in metabolic signalling in humans