Can surgical simulation be used to train detection and classification of neural networks?

Computer-assisted interventions (CAI) aim to increase the effectiveness, precision and repeatability of procedures to improve surgical outcomes. The presence and motion of surgical tools is a key information input for CAI surgical phase recognition algorithms. Vision-based tool detection and recognition approaches are an attractive solution and can be designed to take advantage of the powerful deep learning paradigm that is rapidly advancing image recognition and classification. The challenge for such algorithms is the availability and quality of labelled data used for training. In this Letter, surgical simulation is used to train tool detection and segmentation based on deep convolutional neural networks and generative adversarial networks. The authors experiment with two network architectures for image segmentation in tool classes commonly encountered during cataract surgery. A commercially-available simulator is used to create a simulated cataract dataset for training models prior to performing transfer learning on real surgical data. To the best of authors' knowledge, this is the first attempt to train deep learning models for surgical instrument detection on simulated data while demonstrating promising results to generalise on real data. Results indicate that simulated data does have some potential for training advanced classification methods for CAI systems

Martian Superoxide and Peroxide O2 Release (OR) Assay: A New Technology for Terrestrial and Planetary Applications

This study presents an assay for the detection and quantification of soil metal superoxides and peroxides in regolith and soil. The O2 release (OR) assay is based on the enzymatic conversion of the hydrolysis products of metal oxides to O2, and their quantification by an O2 electrode based on the stoichiometry of the involved reactions: The intermediate product O2 from the hydrolysis of metal superoxides is converted by cytochrome c to O2, and also by superoxide dismutase (SOD) to 1/2 mol O2 and 1/2 mol H2O2, which is then converted by catalase (CAT) to 1/2 mol O2. The product H2O2 from the hydrolysis of metal peroxides and hydroperoxides is converted to 1/2 mol O2 by CAT. The assay-method was validated in a sealed sample chamber using a liquid-phase Clark-type O2 electrode with known concentrations of O2 and H2O2, and with commercial metal superoxide and peroxide mixed with Mars analogue Mojave and Atacama Desert soils. Carbonates and perchlorates, both present on Mars, do not interfere with the assay. The assay lower limit of detection, using luminescence quenching/optical sensing O2-electrodes, is 1 nmol O2 cm(exp. -3) or better. The activity of the assay enzymes SOD and cytochrome c was unaffected up to 6 Gy exposure by gamma-radiation, while CAT retained 100% and 40% of its activity at 3 and 6 Gy, respectively, demonstrating the suitability of these enzymes for planetary missions, e.g., in Mars or Europa

Towards a Computed-Aided Diagnosis System in Colonoscopy: Automatic Polyp Segmentation Using Convolution Neural Networks

Early diagnosis is essential for the successful treatment of bowel cancers including colorectal cancer (CRC), and capsule endoscopic imaging with robotic actuation can be a valuable diagnostic tool when combined with automated image analysis. We present a deep learning rooted detection and segmentation framework for recognizing lesions in colonoscopy and capsule endoscopy images. We restructure established convolution architectures, such as VGG and ResNets, by converting them into fully-connected convolution networks (FCNs), fine-tune them and study their capabilities for polyp segmentation and detection. We additionally use shape-from-shading (SfS) to recover depth and provide a richer representation of the tissue’s structure in colonoscopy images. Depth is incorporated into our network models as an additional input channel to the RGB information and we demonstrate that the resulting network yields improved performance. Our networks are tested on publicly available datasets and the most accurate segmentation model achieved a mean segmentation interception over union (IU) of 47.78% and 56.95% on the ETIS-Larib and CVC-Colon datasets, respectively. For polyp detection, the top performing models we propose surpass the current state-of-the-art with detection recalls superior to 90% for all datasets tested. To our knowledge, we present the first work to use FCNs for polyp segmentation in addition to proposing a novel combination of SfS and RGB that boosts performance

Evidence for presynaptic cholinergic receptors in sympathetic nerves in human dental pulp

The purpose of this study was to determine whether presynaptic cholinergic receptors are present in sympathetic nerves in human dental pulp. Pulp was incubated with [3H]noradrenaline (0.6 mumol/l) for 30 min and then superfused with Krebs' solution at 1.0 ml/min. Electrical stimulation (100 sec, 5 Hz) increased the overflow of [3H]noradrenaline into the superfusate. Carbachol (10 and 100 mumol/l), an agonist of muscarinic receptors, decreased the stimulation-induced (SI) overflow of 3H, an effect blocked by atropine but not hexamethonium. Carbachol, atropine and hexamethonium had no effect on the resting overflow. Nicotine (10 mumol/l) increased the resting overflow and inhibited the SI overflow, although the inhibition was variable. Cytisine, another agonist of nicotinic receptors, also increased the resting overflow, but did not affect the SI overflow. To ascertain whether the actions of nicotine and electrical stimulation were influenced by the release of nitric oxide (NO), the effects of an NO donor and two NO-synthase inhibitors were examined. With the exception of one of the NO-synthase inhibitors (L-NAME), the agents were without effect on the overflow of 3H in the absence or presence of nicotine. It was concluded that sympathetic nerves in human dental pulp possess (a) presynaptic muscarinic receptors that inhibit the SI release of noradrenaline, and (b) nicotinic receptors that evoke the release of noradrenaline and that inhibit the SI release of the transmitter. The results do not point to a significant role for NO in the effects of stimulation or nicotine on the overflow of 3H.D.A.S. Parker, V. Marino, S. Zisimopoulos, I.S. de la Land

Protein and cell wall polysaccharide carbonyl determination by a neutral pH 2,4-dinitrophenylhydrazine-based photometric assay

A new 2,4-dinitrophenylhydrazine (DNPH)-based photometric assay is developed for the quantification of carbonyls in protein samples from any biological source by protein carbonyl-DNPH hydrazone formation at acidic pH in the presence of denaturing urea, and subsequent hydrazone solubilization in the presence of SDS and stabilization from acid hydrolysis at pH 7.0. At this neutral (ntr) pH, interfering unreacted DNPH is uncharged and its thus increased hydrophobicity permits its 100% effective removal from the solubilizate with ethyl acetate/hexane wash. The ntrDNPH assay is more reliable and sensitive than the standard (std) DNPH photometric assay because it eliminates its main limitations: (i) interfering unreacted DNPH (pKa 1.55) that is nonspecifically bound to the TCA (pKa 0.7)-protein pellet is not effectively removed after wash with EtOH: ethyl acetate because it is positively charged, (ii) acid (TCA-induced) hydrolysis of the protein carbonyl-DNPH hydrazone, (iii) sample protein concentration re-determination, (iv) loss of sample acid (TCA)-soluble proteins, (v) DNA interference, and (vi) requires high protein quantity samples (≥ 1 mg). Considering ntrDNPH assay’s very low protein limit (1 µg), its cumulative and functional sensitivities are 2600- and 2000-fold higher than those of the stdDNPH assay, respectively. The present study elucidates the DNA interference mechanism on the stdDNPH assay, and also develops a standardized protocol for sample protein treatment and fractionation (into cytoplasmic/aqueous, membrane/lipid-bound, and histone/DNA-bound proteins; see Supplement section V) in order to ensure reproducible carbonyl determination on defined cell protein fractions, and to eliminate assay interference from protein samples containing (i) Cys sulfenic acid groups (via their neutralization with dithiothreitol), and (ii) DNA (via its removal by streptomycin sulfate precipitation). Lastly, the ntrDNPH assay determines carbonyl groups on cell wall polysaccharides, thus paving the way on studies to investigate cell walls acting as antioxidant defense in plants, fungi, bacteria and lichens. Keywords: Photometric method, 2,4-dinitrophenylhydrazine, Protein carbonyls, Cell wall polysaccharide carbonyls, Oxidative stress, DNA interference, Protein fractionatio

Long acting octreotide in the treatment of advanced hepatocellular cancer and overexpression of somatostatin receptors: Randomized placebo-controlled trial

Aim: To estimate if and to what extent long acting octreotide (LAR) improves survival and quality of life in patients with advanced hepatocellular carcinoma (HCC). Methods: A total of 127 cirrhotics, stages A-B, due to chronic viral infections and with advanced HCC, were enrolled in the study. Scintigraphy with 111Indium labeled octreotide was performed in all cases. The patients with increased accumulation of radionuclear compound were randomized to receive either oral placebo only or octreotide/octreotide LAR only as follows: octreotide 0.5mg s.c. every 8 h for 6 wk, at the end of wk 4-8 octreotide LAR 20 mg i.m. and at the end of wk 12 and every 4 wk octreotide LAR 30mg i.m.. Follow-up was worked out monthly as well as the estimation of quality of life (QLQ-C30 questionnaire). Patients with negative somatostatin receptors (SSTR) detection were followed up in the same manner. Results: Scintigraphy demonstrated SSTR in 61 patients. Thirty were randomized to receive only placebo and 31 only octreotide. A significantly higher survival time was observed for the octreotide group (49 ± 6 wk) as compared to the control group (28 ± 1 wk) and to the SSTR negative group (28 ± 2 wk), LR = 20.39, df = 2, P < 0.01. The octreotide group presented 68.5% lower hazard ratio [95% CI (47.4%-81.2%)]. During the first year, a 22%, 39% and 43% decrease in the QLQ-C30 score was observed in each group respectively. Conclusion: The proposed therapeutic approach has shown to improve the survival and quality of life in SSTR positive patients with advanced HCC. © 2007 The WJG Press. All rights reserved. Indications:30 patients with advanced hepatocellular carcinoma (multinodular 6, massive 20, and diffuse 4) somatostatin receptor-positive and cirrhosis (stage A 11 and stage B 19). Patients:126 patients. Sandostatin group: 30 patients, 20 male and 10 female, mean age 69.4 years. 3 dropouts due to side effects. Placebo (control) group: 30 patients, 22 male and 8 female, mean age 69.5 years. SSTR-negative (SSTR-) group: 66 patients, 36 male and30 female, mean age 69.4 years. Patients were followed up for a period of 4 and 160 weeks. TypeofStudy:This study estimated the extent of improvement of survival rate, with respect to tumor size and alpha-fetoprotein (AFP) levels, and quality of life of patients with advanced hepatocellular carcinoma-somatostatin receptor-positive (HCC-SSTR+) and A-B stage cirrhosis following Sandostatin treatment. Randomized, placebo-controlled clinical trial. DosageDuration:0.5 mg sc tid (=1.5 mg daily) for 6 weeks; at the end of weeks 4 and 8, 20 mg im (as long acting repeatable); and at the end of week 12 and every 4 weeks, 30 mg im (as long acting repeatable). Duration: 12 weeks. Results:At the end of the follow-up period, 1 patient death was recorded. A significantly higher mean survival time was noted for the Sandostatin compared with placebo and SSTR- groups (49 vs. 28 and 28 weeks, respectively; P<0.01). This trend was observed at 6 months, but without reaching statistical significance. After controlling for age, sex, HCC morphological characteristics, etiology, metastases, cirrhosis stage, BCLC stage and AFP levels, the Cox proportional hazard model revealed that patients in the Sandostatin (P<0.01) and placebo (P>0.05) groups had a 68.5% and 7% lower hazard of death, respectively as compared with the SSTR- group. In all 3 groups, a decreasing QLQ-C30 score was observed during the follow-up. During the first 12 months, a 22%, 39%, and 43% decrease was observed in the Sandostatin, placebo, and SSTR- groups, respectively. Sandostatin-treated patients presented a significantly higher QLQ-C30 score as compared with placebo and SSTR- patients (P>0.05). AdverseEffects:A total of 30 adverse events were recorded at the end of follow up. 6 patients developed severe diarrhea leading to Sandostatin withdrawal. FreeText:SSTR determination was conducted in all patients using scintigraphy with 111Indium-labeled octreotide. Patients with increased uptake (Krenning's score 3 and 4) were randomized to receive placebo or Sandostatin. Other tests: AFP levels, liver and renal function, tumor size (dual phase helical computer tomography scan), and QLQ-C30 (quality of life assessment). AuthorsConclusions:The proposed therapeutic approach has shown to improve survival and quality of life in SSTR positive patients with advanced HCC and, despite the high cost, it seems to be an attractive therapeutic option for those who have no possibility for other therapeutic modalities such as liver transplantation, surgical resection, PEI [percutaneous ethanol injection] or TACE [transcatheter arterial chemoembolization]

Protein carbonyl determination by a rhodamine B hydrazide-based fluorometric assay

A new fluorometric assay is presented for the ultrasensitive quantification of total protein carbonyls, and is based on their specific reaction with rhodamine B hydrazide (RBH), and the production of a protein carbonyl-RBH hydrazone the fluorescence of which (at ex/em 560/585 nm) is greatly enhanced by guanidine-HCl. Compared to the fluorescein-5-thiosemicarbazide (FTC)-based fluorometric assay, the RBH assay uses a 24-fold shorter reaction incubation time (1 h) and at least 1000-fold lower protein quantity (2.5 µg), and produces very reliable data that were verified by extensive standardization experiments. The protein carbonyl group detection sensitivity limit of the RBH assay, based on its standard curve, can be as low as 0.4 pmol, and even lower. Counting the very low protein limit of the RBH assay, its cumulative and functional sensitivity is 8500- and 800-fold higher than the corresponding ones for the FTC assay. Neither heme proteins hemoglobin and cytochrome c nor DNA interfere with the RBH assay. Keywords: Fluorometric method, Rhodamine B hydrazide, Protein carbonyls, Protein oxidation, Oxidative stress, DN