Precision measurement of carbon isotope ratio in exhaled breath for the detection of helicobacter pylori

The utility of breath trace compounds as bio-markers for various physiological conditions has long been exploited for the diagnosis of various diseases. Urea breath tests have been adopted as the gold standard for the detection of Helicobacter pylori which is a primary cause for acute gastritis and peptic ulcers. In these tests, small changes in the ratio of stable CO2 isotopomers, 13CO2 and 12CO2, present in exhaled breath are measured precisely and this is conventionally done by using anIsotope Ratio Mass Spectrometer. However, the huge cost and complexity involved in operating these instruments has restricted their widespread use. A viable and low cost alternative is offered by instruments employing non-dispersive infrared absorption techniques. The feasibility of such an instrument has been explored in this work.The instrument presented here is a two channel isotope ratiometer that performs whole band integrated absorption measurements. Detection is based on a novel feedback mechanism whereby an imbalance in the channel absorptions causes the pathlength along one of the channels to be altered in order to bring the system back to balance. This change in ratio of pathlengths is directly related to thechange in the 13CO2/12CO2 concentration. Significant amount of work has already been done to investigate the effects of interferences from coincident absorption bands and other spectral effects that can lead to spurious results.A comprehensive description of the overall system design, development and performance evaluation of the first prototype instrument has been presented here. This involved significant computer modeling and simulations and the results were verified experimentally. These results provided sufficient evidence to suggest the feasibility of such an instrument as a diagnostic tool. It was also concluded that some design improvements were required to circumvent issues related to pathlength variation and a list of recommendations has been provided for this purpose. On the basis of the results obtained as part of this research endeavour, it was concluded that the non-dispersive instrument design presented here can form the basis for a low cost commercial alternative for performing carbon isotope ratio breath tests.</p

Role of Microsolvation and Quantum Effects in the Accurate Prediction of Kinetic Isotope Effects: The Case of Hydrogen Atom Abstraction in Ethanol by Atomic Hydrogen in Aqueous Solution

Hydrogen abstraction from ethanol by atomic hydrogen in aqueous solution is studied using two theoretical approaches: the multipath variational transition state theory (MP-VTST) and a path-integral formalism in combination with free-energy perturbation and umbrella sampling (PI-FEP/UM). The performance of the models is compared to experimental values of H kinetic isotope effects (KIE). Solvation models used in this study ranged from purely implicit, via mixed–microsolvation treated quantum mechanically via the density functional theory (DFT) to fully explicit representation of the solvent, which was incorporated using a combined quantum mechanical-molecular mechanical (QM/MM) potential. The effects of the transition state conformation and the position of microsolvating water molecules interacting with the solute on the KIE are discussed. The KIEs are in good agreement with experiment when MP-VTST is used together with a model that includes microsolvation of the polar part of ethanol by five or six water molecules, emphasizing the importance of explicit solvation in KIE calculations. Both, MP-VTST and PI-FEP/UM enable detailed characterization of nuclear quantum effects accompanying the hydrogen atom transfer reaction in aqueous solutionThis work was partially supported by the National Science Center in Poland (Sonata BIS grant UMO-2014/14/E/ST4/00041) and in part by PLGrid Infrastructure (Poland). S.K. acknowledges the Erasmus+ programme within which his 3-month project conducted at the University of Santiago de Compostela was possible. A.F-.R. thanks the Consellería de Cultura, Educación e Ordenación Universitaria (Axuda para Consolidación e Estructuración de unidades de investigación competitivas do Sistema Universitario de Galicia, Xunta de Galicia ED431C 2017/17 & Centro singular de investigación de Galicia acreditación 2016-2019, ED431G/09) and the European Regional Development Fund (ERDF). D.F-.C. also thanks Xunta de Galicia for financial support through a postdoctoral grantS

AutoML accurately predicts endovascular mechanical thrombectomy in acute large vessel ischemic stroke

Background and objectiveAutomated machine learning or autoML has been widely deployed in various industries. However, their adoption in healthcare, especially in clinical settings is constrained due to a lack of clear understanding and explainability. The aim of this study is to utilize autoML for the prediction of functional outcomes in patients who underwent mechanical thrombectomy and compare it with traditional ML models with a focus on the explainability of the trained models.MethodsA total of 156 patients of acute ischemic stroke with Large Vessel Occlusion (LVO) who underwent mechanical thrombectomy within 24 h of stroke onset were included in the study. A total of 34 treatment variables including clinical, demographic, imaging, and procedure-related data were extracted. Various conventional machine learning models such as decision tree classifier, logistic regression, random forest, kNN, and SVM as well as various autoML models such as AutoGluon, MLJAR, Auto-Sklearn, TPOT, and H2O were used to predict the modified Rankin score (mRS) at the time of patient discharge and 3 months follow-up. The sensitivity, specificity, accuracy, and AUC for traditional ML and autoML models were compared.ResultsThe autoML models outperformed the traditional ML models. For the prediction of mRS at discharge, the highest testing accuracy obtained by traditional ML models for the decision tree classifier was 74.11%, whereas for autoML which was obtained through AutoGluon, it showed an accuracy of 88.23%. Similarly, for mRS at 3 months, the highest testing accuracy of traditional ML was that of the SVM classifier at 76.5%, whereas that of autoML was 85.18% obtained through MLJAR. The 24-h ASPECTS score was the most important predictor for mRS at discharge whereas for prediction of mRS at 3 months, the most important factor was mRS at discharge.ConclusionAutomated machine learning models based on multiple treatment variables can predict the functional outcome in patients more accurately than traditional ML models. The ease of clinical coding and deployment can assist clinicians in the critical decision-making process. We have developed a demo application which can be accessed at https://mrs-score-calculator.onrender.com/

Non-invasive diagnostic tests for Helicobacter pylori infection

BACKGROUND: Helicobacter pylori (H pylori) infection has been implicated in a number of malignancies and non-malignant conditions including peptic ulcers, non-ulcer dyspepsia, recurrent peptic ulcer bleeding, unexplained iron deficiency anaemia, idiopathic thrombocytopaenia purpura, and colorectal adenomas. The confirmatory diagnosis of H pylori is by endoscopic biopsy, followed by histopathological examination using haemotoxylin and eosin (H & E) stain or special stains such as Giemsa stain and Warthin-Starry stain. Special stains are more accurate than H & E stain. There is significant uncertainty about the diagnostic accuracy of non-invasive tests for diagnosis of H pylori. OBJECTIVES: To compare the diagnostic accuracy of urea breath test, serology, and stool antigen test, used alone or in combination, for diagnosis of H pylori infection in symptomatic and asymptomatic people, so that eradication therapy for H pylori can be started. SEARCH METHODS: We searched MEDLINE, Embase, the Science Citation Index and the National Institute for Health Research Health Technology Assessment Database on 4 March 2016. We screened references in the included studies to identify additional studies. We also conducted citation searches of relevant studies, most recently on 4 December 2016. We did not restrict studies by language or publication status, or whether data were collected prospectively or retrospectively. SELECTION CRITERIA: We included diagnostic accuracy studies that evaluated at least one of the index tests (urea breath test using isotopes such as13C or14C, serology and stool antigen test) against the reference standard (histopathological examination using H & E stain, special stains or immunohistochemical stain) in people suspected of having H pylori infection. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the references to identify relevant studies and independently extracted data. We assessed the methodological quality of studies using the QUADAS-2 tool. We performed meta-analysis by using the hierarchical summary receiver operating characteristic (HSROC) model to estimate and compare SROC curves. Where appropriate, we used bivariate or univariate logistic regression models to estimate summary sensitivities and specificities. MAIN RESULTS: We included 101 studies involving 11,003 participants, of which 5839 participants (53.1%) had H pylori infection. The prevalence of H pylori infection in the studies ranged from 15.2% to 94.7%, with a median prevalence of 53.7% (interquartile range 42.0% to 66.5%). Most of the studies (57%) included participants with dyspepsia and 53 studies excluded participants who recently had proton pump inhibitors or antibiotics.There was at least an unclear risk of bias or unclear applicability concern for each study.Of the 101 studies, 15 compared the accuracy of two index tests and two studies compared the accuracy of three index tests. Thirty-four studies (4242 participants) evaluated serology; 29 studies (2988 participants) evaluated stool antigen test; 34 studies (3139 participants) evaluated urea breath test-13C; 21 studies (1810 participants) evaluated urea breath test-14C; and two studies (127 participants) evaluated urea breath test but did not report the isotope used. The thresholds used to define test positivity and the staining techniques used for histopathological examination (reference standard) varied between studies. Due to sparse data for each threshold reported, it was not possible to identify the best threshold for each test.Using data from 99 studies in an indirect test comparison, there was statistical evidence of a difference in diagnostic accuracy between urea breath test-13C, urea breath test-14C, serology and stool antigen test (P = 0.024). The diagnostic odds ratios for urea breath test-13C, urea breath test-14C, serology, and stool antigen test were 153 (95% confidence interval (CI) 73.7 to 316), 105 (95% CI 74.0 to 150), 47.4 (95% CI 25.5 to 88.1) and 45.1 (95% CI 24.2 to 84.1). The sensitivity (95% CI) estimated at a fixed specificity of 0.90 (median from studies across the four tests), was 0.94 (95% CI 0.89 to 0.97) for urea breath test-13C, 0.92 (95% CI 0.89 to 0.94) for urea breath test-14C, 0.84 (95% CI 0.74 to 0.91) for serology, and 0.83 (95% CI 0.73 to 0.90) for stool antigen test. This implies that on average, given a specificity of 0.90 and prevalence of 53.7% (median specificity and prevalence in the studies), out of 1000 people tested for H pylori infection, there will be 46 false positives (people without H pylori infection who will be diagnosed as having H pylori infection). In this hypothetical cohort, urea breath test-13C, urea breath test-14C, serology, and stool antigen test will give 30 (95% CI 15 to 58), 42 (95% CI 30 to 58), 86 (95% CI 50 to 140), and 89 (95% CI 52 to 146) false negatives respectively (people with H pylori infection for whom the diagnosis of H pylori will be missed).Direct comparisons were based on few head-to-head studies. The ratios of diagnostic odds ratios (DORs) were 0.68 (95% CI 0.12 to 3.70; P = 0.56) for urea breath test-13C versus serology (seven studies), and 0.88 (95% CI 0.14 to 5.56; P = 0.84) for urea breath test-13C versus stool antigen test (seven studies). The 95% CIs of these estimates overlap with those of the ratios of DORs from the indirect comparison. Data were limited or unavailable for meta-analysis of other direct comparisons. AUTHORS' CONCLUSIONS: In people without a history of gastrectomy and those who have not recently had antibiotics or proton ,pump inhibitors, urea breath tests had high diagnostic accuracy while serology and stool antigen tests were less accurate for diagnosis of Helicobacter pylori infection.This is based on an indirect test comparison (with potential for bias due to confounding), as evidence from direct comparisons was limited or unavailable. The thresholds used for these tests were highly variable and we were unable to identify specific thresholds that might be useful in clinical practice.We need further comparative studies of high methodological quality to obtain more reliable evidence of relative accuracy between the tests. Such studies should be conducted prospectively in a representative spectrum of participants and clearly reported to ensure low risk of bias. Most importantly, studies should prespecify and clearly report thresholds used, and should avoid inappropriate exclusions

A VCSEL based system for on-site monitoring of low level methane emission

Continuous monitoring of methane emissions has assumed greater significance in the recent past due to increasing focus on global warming issues. Many industries have also identified the need for ppm level methane measurement as a means of gaining carbon credits. Conventional instruments based on NDIR spectroscopy are unable to offer the high selectivity and sensitivity required for such measurements. Here we discuss the development of a robust VCSEL based system for accurate low level measurements of methane. A possible area of application is the measurement of residual methane whilst monitoring the output of flare stacks and exhaust gases from methane combustion engines. The system employs a Wavelength Modulation Spectroscopy (WMS) scheme with second harmonic detection at 1651 nm. Optimum modulation frequency and ramp rates were chosen to maintain high resolution and fast response times which are vital for the intended application. Advanced data processing techniques were used to achieve long term sensitivity of the order of 10-5 in absorbance. The system is immune to cross interference from other gases and its inherent design features makes it ideal for large scale commercial production. The instrument maintains its calibration and offers a completely automated continuous monitoring solution for remote on site deployment

Can Alkaline Hydrolysis of γ-HCH Serve as a Model Reaction to Study Its Aerobic Enzymatic Dehydrochlorination by LinA?

Hexachlorocyclohexane (HCH) isomers constitute a group of persistent organic pollutants. Their mass production and treatment have led to a global environmental problem that continues to this day. The characterization of modes of degradation of HCH by isotope fractionation is a current challenge. Multi isotope fractionation analysis provides a concept to characterize the nature of enzymatic and chemical transformation reactions. The understanding of the kinetic isotope effects (KIE) on bond cleavage reaction contributes to analyses of the mechanism of chemical and enzymatic reactions. Herein, carbon, chlorine, and hydrogen kinetic isotope effects are measured and predicted for the dehydrochlorination reaction of &gamma;-HCH promoted by the hydroxyl ion in aqueous solution. Quantum mechanical (QM) microsolvation with an implicit solvation model and path integral formalism in combination with free-energy perturbation and umbrella sampling (PI-FEP/UM) and quantum mechanical/molecular mechanical QM/MM potentials for including solvent effects as well as calculating isotope effects are used and analyzed with respect to their performance in reproducing measured values. Reaction characterization is discussed based on the magnitudes of obtained isotope effects. The comparative analysis between the chemical dehydrochlorination of &gamma;-HCH in aqueous media and catalyzed reaction by dehydrochlorinase, LinA is presented and discussed. Based on the values of isotope effects, these two processes seem to occur via the same net mechanism

Development of low cost instrumentation for non-invasive detection of Helicobacter Pylori

A new clinical diagnostic instrument for urea breath test (UBT) based non-invasive detection of Helicobacter Pylori is presented here. Its compact and low cost design makes it an economical and commercial alternative for the more expensive Isotope Ratio Mass Spectrometer (IRMS). The instrument is essentially a two channel non-dispersive IR spectrometer that performs high precision ratio measurements of the two carbon isotopomers () present in exhaled breath. A balanced absorption system configuration was designed where the two channel path lengths would roughly be in the ratio of their concentrations. Equilibrium between the transmitted channel intensities was maintained by using a novel feedback servo mechanism to adjust the length of the 13C channel cell. Extensive computational simulations were performed to study the effect of various possible interferents and their results were considered in the design of the instrument so as to achieve the desired measurement precision of 1%. Specially designed gas cells and a custom made gas filling rig were also developed. A complete virtual interface for both instrument control and data acquisition was implemented in LABVIEW. Initial tests were used to validate the theory and a basic working device was demonstrated

Current status of stenting in intracranial atherosclerotic disease: The story thus far and the way ahead

Despite medical management, symptomatic intracranial atherosclerotic disease has a high risk of stroke and death. This unacceptably high rate has provided the impetus for development and continuous advancements in the field of endovascular revascularization. From early attempts at angioplasty alone to state-of-the art stents including self-expanding and drug-eluting stents specially designed for the cerebral vessels, developments in this field has come a long way. As we stand today, however, there are still mixed views on the use of these endovascular techniques vs aggressive medical management. In this article, we review the mechanisms of stroke in patients with intracranial atherosclerotic disease and review the current status of stenting in this condition. A brief discussion of the important clinical and procedural considerations is also provided along with a mention of the ongoing trials likely to provide valuable information on the future of stenting