Machine learning based detection of T-wave alternans in real ambulatory conditions.

BACKGROUND AND OBJECTIVE: T-wave alternans (TWA) is a fluctuation in the repolarization morphology of the ECG. It is associated with cardiac instability and sudden cardiac death risk. Diverse methods have been proposed for TWA analysis. However, TWA detection in ambulatory settings remains a challenge due to the absence of standardized evaluation metrics and detection thresholds. METHODS: In this work we use traditional TWA analysis signal processing-based methods for feature extraction, and two machine learning (ML) methods, namely, K-nearest-neighbor (KNN) and random forest (RF), for TWA detection, addressing hyper-parameter tuning and feature selection. The final goal is the detection in ambulatory recordings of short, non-sustained and sparse TWA events. RESULTS: We train ML methods to detect a wide variety of alternant voltage from 20 to 100 µV, i.e., ranging from non-visible micro-alternans to TWA of higher amplitudes, to recognize a wide range in concordance to risk stratification. In classification, RF outperforms significantly the recall in comparison with the signal processing methods, at the expense of a small lost in precision. Despite ambulatory detection stands for an imbalanced category context, the trained ML systems always outperform signal processing methods. CONCLUSIONS: We propose a comprehensive integration of multiple variables inspired by TWA signal processing methods to fed learning-based methods. ML models consistently outperform the best signal processing methods, yielding superior recall scores.

Characterization of noise in long-term ECG monitoring with machine learning based on clinical criteria.

Noise and artifacts affect strongly the quality of the electrocardiogram (ECG) in long-term ECG monitoring (LTM), making some of its parts impractical for diagnosis. The clinical severity of noise defines a qualitative quality score according to the manner clinicians make the interpretation of the ECG, in contrast to assess noise from a quantitative standpoint. So clinical noise refers to a scale of different levels of qualitative severity of noise which aims at elucidating which ECG fragments are valid to achieve diagnosis from a clinical point of view, unlike the traditional approach, which assesses noise in terms of quantitative severity. This work proposes the use of machine learning (ML) techniques to categorize different qualitative noise severity using a database annotated according to a clinical noise taxonomy as gold standard. A comparative study is carried out using five representative ML methods, namely, K neareast neighbors, decision trees, support vector machine, single-layer perceptron, and random forest. The models are fed by signal quality indexes characterizing the waveform in time and frequency domains, as well as from a statistical viewpoint, to distinguish between clinically valid ECG segments from invalid ones. A solid methodology to prevent overfitting to both the dataset and the patient is developed, taking into account balance of classes, patient separation, and patient rotation in the test set. All the proposed learning systems have demonstrated good classification performance, attaining a recall, precision, and F1 score up to 0.78, 0.80, and 0.77, respectively, in the test set by a single-layer perceptron approach. These systems provide a classification solution for assessing the clinical quality of the ECG taken from LTM recordings. Graphical Abstract Clinical Noise Severity Classification based on Machine Learning techniques towards Long-Term ECG Monitoring.

Machine Learning approach for TWA detection relying on ensemble data design.

Background and objective: T-wave alternans (TWA) is a fluctuation of the ST-T complex of the surface electrocardiogram (ECG) on an every-other-beat basis. It has been shown to be clinically helpful for sudden cardiac death stratification, though the lack of a gold standard to benchmark detection methods limits its application and impairs the development of alternative techniques. In this work, a novel approach based on machine learning for TWA detection is proposed. Additionally, a complete experimental setup is presented for TWA detection methods benchmarking. Methods: The proposed experimental setup is based on the use of open-source databases to enable experiment replication and the use of real ECG signals with added TWA episodes. Also, intra-patient overfitting and class imbalance have been carefully avoided. The Spectral Method (SM), the Modified Moving Average Method (MMA), and the Time Domain Method (TM) are used to obtain input features to the Machine Learning (ML) algorithms, namely, K Nearest Neighbor, Decision Trees, Random Forest, Support Vector Machine and Multi-Layer Perceptron. Results: There were not found large differences in the performance of the different ML algorithms. Decision Trees showed the best overall performance (accuracy 0.88 ± 0.04 , precision 0.89 ± 0.05 , Recall 0.90 ± 0.05 , F1 score 0.89 ± 0.03 ). Compared to the SM (accuracy 0.79, precision 0.93, Recall 0.64, F1 score 0.76) there was an improvement in every metric except for the precision. Conclusions: In this work, a realistic database to test the presence of TWA using ML algorithms was assembled. The ML algorithms overall outperformed the SM used as a gold standard. Learning from data to identify alternans elicits a substantial detection growth at the expense of a small increment of the false alarm.

Species Distribution in Bicontinuous Phase Systems for Enhanced Oil Recovery Probed by Single-Sided NMR.

Multiphase aqueous-organic systems where a bicontinuous phase is in equilibrium with an excess organic and aqueous phase find various applications in industry. These systems─also known as Winsor III─are complex not only for the different phases that develop therein but also because they are multicomponent systems. In this work, we explore for the first time the use of a benchtop low-field single-sided NMR to determine the species distribution in Winsor III systems. The proposed methodology provides information at macroscopic and microscopic levels. In particular, we show the use of single-sided NMR to determine the phases' dimensions and the species distribution in a polymer-based bicontinuous system. The phases' dimensions and limits can be resolved with micrometric precision and are indicative of the bicontinuous phase stability. The species distribution is determined by means of spatially resolved NMR relaxation and diffusion experiments. It was observed that the salinity of the aqueous phase also impacts the species distribution in the bicontinuous system. Experiments show that the additive and the polymer are mainly located in the bicontinuous phase. As the salinity of the aqueous phase increases, the amount of organic components in the bicontinuous phase decreases as a consequence of the species distribution in the system. This influences the total amount of recovered organic liquid from the organic phase. The information is obtained in a relatively fast experiment and is relevant to the system's possible applications, such as enhanced oil recovery (EOR). This methodology is not only circumscribed to its application in EOR but can also be applied to the study of any emulsion or microemulsion systems without sample size or geometry constraints.

Physiologically-based pharmacokinetic modelling and dosing evaluation of gentamicin in neonates using PhysPK.

Each year, infections caused around the 25% of neonatal deaths. Early empirical treatments help to reduce this mortality, although optimized dosing regimens are still lacking. The aims were to develop and validate a gentamicin physiologically-based pharmacokinetic (PBPK) model and then potentially explore dosing regimens in neonates using pharmacokinetic and pharmacodynamic criteria. The PBPK model developed consisted of 2 flow-limited tissues: kidney and other tissues. It has been implemented on a new tool called PhysPK, which allows structure reusability and evolution as predictive engine in Model-Informed Precision Dosing (MIPD). Retrospective pharmacokinetic information based on serum levels data from 47 neonates with gestational age between 32 and 39 weeks and younger than one-week postnatal age were used for model validation. The minimal PBPK model developed adequately described the gentamicin serum concentration-time profile with an average fold error nearly 1. Extended interval gentamicin dosing regimens (6 mg/kg q36h and 6 mg/kg q48h for term and preterm neonates, respectively) showed efficacy higher than 99% with toxicity lower than 10% through Monte Carlo simulation evaluations. The gentamicin minimal PBPK model developed in PhysPK from literature information, and validated in preterm and term neonates, presents adequate predictive performance and could be useful for MIPD strategies in neonates.

On Power Line Positioning Systems.

Power line infrastructure is available almost everywhere. Positioning systems aim to estimate where a device or target is. Consequently, there may be an opportunity to use power lines for positioning purposes. This survey article reports the different efforts, working principles, and possibilities for implementing positioning systems relying on power line infrastructure for power line positioning systems (PLPS). Since Power Line Communication (PLC) systems of different characteristics have been deployed to provide communication services using the existing mains, we also address how PLC systems may be employed to build positioning systems. Although some efforts exist, PLPS are still prospective and thus open to research and development, and we try to indicate the possible directions and potential applications for PLPS.

Piperidine-Iodine as Efficient Dual Catalyst for the One-Pot, Three-Component Synthesis of Coumarin-3-Carboxamides.

A simple and efficient one-pot, three-component synthetic method for the preparation of coumarin-3-carboxamides was carried out by the reaction of salicylaldehyde, aliphatic primary/secondary amines, and diethylmalonate. The protocol employs piperidine-iodine as a dual system catalyst and ethanol, a green solvent. The main advantages of this approach are that it is a metal-free and clean reaction, has low catalyst loading, and requires no tedious workup.

NMR characterization of structure and moisture sorption dynamics of damaged starch granules.

Among the many biopolymers that constitute food products, starch is one of the most common. Starch granules are often damaged in the milling process, which affects the final product quality, mainly due to changes in water adsorption properties. In this work, the crystallinity degree of wheat starch samples as a function of the mechanical damage is determined by low field 1H NMR. We also introduce the use of single-sided NMR to determine granular swelling, water distribution and sorption dynamics of the samples. Results show that the crystallinity of the samples decreases with the milling. We also observed that swelling index and sorption capacity values are higher in the milled samples than in the native starch. Our experiments show how single-sided NMR is a valuable tool to provide information on dynamic processes not only in starch, but also in many carbohydrate polymeric samples with the additional benefit of spatial resolution.

Comparison of experimental times in T1-D and D-T2 correlation experiments in single-sided NMR.

Diffusion-relaxation correlation experiments in nuclear magnetic resonance are a powerful technique for the characterization of fluid dynamics in confined geometries or soft matter, in which relaxation may be either spin-spin (T2) or spin-lattice (T1). The general approach is to acquire a set of bidimensional data in which diffusion is codified by the evolution of the magnetization with either Hahn or stimulated echoes (STE) in the presence of a constant magnetic field gradient. While T2 is codified by a Carr-Purcell-Meiboom-Gil (CPMG) sequence, T1 is either encoded by saturation or inversion-recovery methods. In this work, we analyse the measurement time of diffusion-relaxation times in single-sided NMR and show that T1-D acquisition is always shorter than D-T2. Depending on the hardware characteristics, this time reduction can be up to an order of magnitude. We present analytical calculations and examples in model porous media saturated with water and in a dairy product.

Brote de parotiditis relacionado con el fumar en un narguile de uso público / Mumps virus outbreak related to a water pipe (narghile) shared smoking

Introducción: En este estudio se describe un brote de parotiditis que afectó a un grupo de jóvenes que compartieron un narguile para fumar. Métodos: La notificación de un caso de parotiditis dio lugar a una investigación epidemiológica. Se recabó información de otras 6personas sintomáticas que se habían reunido en una discoteca en la que habían fumado en un mismo narguile. Se obtuvieron muestras de saliva para RT-PCR y sangre para serología de parotiditis de otros 3de estos casos. Las muestras RT-PCR positivas se genotipificaron por secuenciación. Resultados: Los 7 pacientes residían en 3municipios diferentes. Hacía más de un mes que no habían coincidido hasta que estuvieron en la discoteca. Cuatro casos se confirmaron por RT-PCR o IgM específica. La investigación genómica mostró secuencias idénticas. Conclusiones: Este brote es consecuencia de un uso compartido de un narguile. Consideramos que se debería regular la utilización pública de estas pipas.(AU)

Introduction: This study describes a mumps outbreak among a group of young people who shared a same narghile to smoking. Saliva and blood samples were obtained from 3cases for RT-PCR and serology respectively. Methods: The notification of a mumps case started an epidemiological investigation. Information of other 6additional symptomatic persons who had gathered with the case in a discotheque where they smoking in a same narghile was achieved. RT-PCR positive samples were genotyped by sequencing. Results: The 7patients resided in 3different municipalities, and they do not have get together for more than a month until the meeting in the discotheque. Four cases were confirmed by RT-PCR and/or IgM determinations. The genomic investigation showed identical nucleic sequences. Conclusions: This outbreak is consequence of the common use of a narghile to smoking. The public usage of these water pipes should be regulated.(AU)

Mumps virus outbreak related to a water pipe (narghile) shared smoking.

INTRODUCTION: This study describes a mumps outbreak among a group of young people who shared a same narghile to smoking. Saliva and blood samples were obtained from 3 cases for RT-PCR and serology respectively. METHODS: The notification of a mumps case started an epidemiological investigation. Information of other 6 additional symptomatic persons who had gathered with the case in a discotheque where they smoking in a same narghile was achieved. RT-PCR positive samples were genotyped by sequencing. RESULTS: The 7 patients resided in 3 different municipalities, and they do not have get together for more than a month until the meeting in the discotheque. Four cases were confirmed by RT-PCR and/or IgM determinations. The genomic investigation showed identical nucleic sequences. CONCLUSIONS: This outbreak is consequence of the common use of a narghile to smoking. The public usage of these water pipes should be regulated.

Lipid Accumulation Product Is More Related to Insulin Resistance than the Visceral Adiposity Index in the Maracaibo City Population, Venezuela.

BACKGROUND: Visceral adiposity is related to insulin resistance (IR), a metabolic state considered as a risk factor for other cardiometabolic diseases. In that matter, mathematical indexes such as the visceral adiposity index (VAI) and the lipid accumulation product (LAP) could indirectly assess IR based on visceral adiposity. OBJECTIVE: To evaluate the association and diagnostic accuracy of VAI and LAP to diagnose IR in the adult population of Maracaibo city. METHODS: This is a cross-sectional descriptive study with multistage sampling. Receiver operating characteristic (ROC) curves were built to determine VAI and LAP cutoff points to predict IR. A set of logistic regression models was constructed according to sociodemographic, psychobiologic, and metabolic variables. RESULTS: 1818 subjects were evaluated (51.4% women). The area under the curve (AUC) values for LAP and VAI were 0.689 (0.665-0.714) and 0.645 (0.619-0.670), respectively. Both indexes showed a higher IR risk in the upper tertile in bivariate analysis. However, in the logistic regression analysis for the IR risk, only the 2nd (OR: 1.91; 95% CI: 1.37-2.65; p < 0.01) and 3rd (OR: 5.40; 95% CI: 3.48-8.39; p < 0.01) LAP tertiles showed a significant increase. This behaviour was also observed after adjusting for hs-C-reactive protein (hs-CPR). CONCLUSION: Although both indexes show a low predictive capacity in individuals with IR in the Maracaibo city population, the LAP index was more strongly associated with IR.

Potential Role of Bioactive Lipids in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that involves a pathological inflammatory response against articular cartilage in multiple joints throughout the body. It is a complex disorder associated with comorbidities such as depression, lymphoma, osteoporosis, and cardiovascular disease (CVD), which significantly deteriorate patients' quality of life and prognosis. This has ignited a large initiative to elucidate the physiopathology of RA, aiming to identify new therapeutic targets and approaches in its multidisciplinary management. Recently, various lipid bioactive products have been proposed to have an essential role in this process, including eicosanoids, specialized pro-resolving mediators, phospholipids/sphingolipids, and endocannabinoids. Dietary interventions using omega-3 polyunsaturated fatty acids or treatment with synthetic endocannabinoid agonists have been shown to significantly ameliorate RA symptoms. Indeed, the modulation of lipid metabolism may be crucial in the pathophysiology and treatment of autoimmune diseases.

Formulation and Performance Analysis of Broadband and Narrowband OFDM-Based PLC Systems.

The aim of this paper is to formulate the physical layer of the broadband and narrowband power line communication (PLC) systems described in standards IEEE 1901 and IEEE 1901.2, which address new communication technologies over electrical networks for Smart Grid and Internet of Things applications. Specifically, this paper presents a mathematical formulation by means of matrices of a transmitter and receiver system based on windowed OFDM. The proposed formulation is essential for obtaining the input-output relation, as well as an analysis of the interference present in the system. It is very useful for simulating PLC systems using software designed to operate primarily on whole matrices and arrays, such as Matlab. In addition, it eases the analysis and design of different receiver configurations, simply by modifying or adding a matrix. Since the relevant standards only describe the blocks corresponding to the transmitter, and leave the set-up of the receiver open to the manufacturer, we analysed four different possible schemes that include window functions in different configurations. In simulations, the behaviour of each of these schemes is analysed in terms of bit error and achievable data rates using artificial and real noises.

Calcipotriol/betamethasone dipropionate aerosol foam for the treatment of psoriasis vulgaris: a review of real-world evidence (RWE).

BACKGROUND: Randomized controlled trials (RCTs) demonstrated the advantages of an aerosol foam formulation of calcipotriol/betamethasone dipropionate (Cal/BD) in patients with psoriasis. In this review, we investigated whether such benefits could also be obtained in real-world clinical practice. METHODS: PubMed was searched for studies reporting real-world data in patients with psoriasis treated with Cal/BD aerosol foam. RESULTS: Three large real-world studies with Cal/BD aerosol foam were identified: a prospective non-interventional study from Germany, a medical chart review from the US, and a retrospective non-interventional study from Spain. Some key findings included the following: high levels of adherence to treatment (82-93%); after 4 weeks, about 50% of patients achieved complete/almost complete responses; at final assessment, 85-95% of patients were extremely satisfied/very satisfied/satisfied with Cal/BD aerosol foam; all healthcare providers were satisfied or somewhat satisfied with the efficacy of Cal/BD foam and they reported similar findings for symptom improvements (itch, pain, erythema/redness, flaking, and plaque thickness). Global ratings by investigators/healthcare providers for symptom control, overall efficacy and the emotional status of patients were also very high (75-100%). CONCLUSION: The results from real-world studies undertaken in diverse healthcare systems reinforce the positive findings reported in RCTs with Cal/BD aerosol foam in patients with psoriasis.

Mumps virus outbreak related to a water pipe (narghile) shared smoking. / Brote de parotiditis relacionado con el fumar en un narguile de uso público.

INTRODUCTION: This study describes a mumps outbreak among a group of young people who shared a same narghile to smoking. Saliva and blood samples were obtained from 3cases for RT-PCR and serology respectively. METHODS: The notification of a mumps case started an epidemiological investigation. Information of other 6additional symptomatic persons who had gathered with the case in a discotheque where they smoking in a same narghile was achieved. RT-PCR positive samples were genotyped by sequencing. RESULTS: The 7patients resided in 3different municipalities, and they do not have get together for more than a month until the meeting in the discotheque. Four cases were confirmed by RT-PCR and/or IgM determinations. The genomic investigation showed identical nucleic sequences. CONCLUSIONS: This outbreak is consequence of the common use of a narghile to smoking. The public usage of these water pipes should be regulated.

Role of Histamine as a Peripheral Sympathetic Neuromediator and its Interrelation with Substance P.

This article is an educational review about the fundamental aspects related to the proposal of the existence of a peripheral sympathetic reflex regulated by histamine, through its effect on presynaptic H3 type receptors, under the interaction of a sensory neuron that would be mediated by Substance P. In this respect, we consider it useful to highlight the role of histamine, so we discuss some aspects about its history, metabolism, and function, as well as its interaction with H3 type receptors that are considered as neuroreceptors, which define and typify it as a neuromediator at both levels of the nervous system, central and peripheral.

The effectiveness and safety of ixekizumab in psoriasis patients under clinical practice conditions: A Spanish multicentre retrospective study.

The objective of the study was to evaluate efficacy and safety of ixekizumab in psoriasis patients under clinical practice conditions. Observational, retrospective, multicentre study that included patients with ixekizumab from March 2017 to March 2019. ≥ 90% reduction in the Psoriasis Area and Severity Index (PASI 90) and absolute PASI <2 were the parameters used to assess treatment response. Adverse events (AEs) were collected. Of the 301 patients included, 111 were women (36.9%), mean age was 48.5 (±13.5) years. Mean baseline PASI score was 13.5 (±7.7). More than half of the patients (68.5%) had received at least one biological drug before. At 3 months, 208 (76.5%) patients achieved PASI <2 and 156 (57.3%) PASI 90. At 12 months, 130 (73.4%) patients achieved absolute PASI <2 and 104 (58.7%) PASI 90. Multivariate analysis revealed that prior use of biologics was influential in achieving PASI <2 at both 3 and 12 months (OR 2.82, P = .006; OR 9.51, P < .001, respectively). Sixty-five patients (21.59%) exhibited at least one AE, injection site reaction was the most common (39; 36.8%). Likewise in trials, ixekizumab displayed an excellent profile of safety and efficacy also in real-life. Effectiveness appears superior in biologic-naive patients.

Exploring Phytotherapeutic Alternatives for Obesity, Insulin Resistance and Diabetes Mellitus.

At present, the pathologic spectrum of obesity-insulin resistance (IR)-diabetes mellitus (DM) represents not only a pressing matter in public health but also a paramount object of study in biomedical research, as they constitute major risk factors for cardiovascular disease (CVD), and other chronic non-communicable diseases (NCD). Phytotherapy, the use of medicinal herbs (MH) with treatment purposes, offers a wide array of opportunities for innovation in the management of these disorders; mainly as pharmacological research on small molecules accumulates. Several MH has displayed varied mechanisms of action relevant to the pathogenesis of obesity, IR and DM, including immunological and endocrine modulation, reduction of inflammation and oxidative stress (OS), regulation of appetite, thermogenesis and energy homeostasis, sensitisation to insulin function and potentiation of insulin release, among many others. However, the clinical correlates of these molecular phenomena remain relatively uncertain, with only a handful of MH boasting convincing clinical evidence in this regard. This review comprises an exploration of currently available preclinical and clinical research on the role of MH in the management of obesity, IR, and DM.

Role of Dietary Polyphenols in Adipose Tissue Browning: A Narrative Review.

Lifestyle modifications such as energy restriction and increased physical activity are highly effective in the management of obesity. However, adherence to these therapeutic approaches is poor. On the other hand, synthetic drugs used for obesity control are plagued by adverse effects. Despite these failures, adipose tissue is still an attractive therapeutic target for novel molecules, and thus, the characterisation of new and safer anti-obesity drugs is of significant interest. For this reason, in recent years, phenolic constituents of diverse plants have drawn much attention due to their health-promoting properties, opening new research lines related to brown adipose tissue activation and white adipose tissue (WAT) browning. The goal is to increase energy expenditure levels through thermogenic activity activation by multiple factors, like polyphenols. The suggested mechanisms by which polyphenols can modulate thermogenesis include Nor-epinephrine/Catechol-O-Methyl-Transferase (NE/COMT) inhibition, PPARγ co-activator alpha (PGC-1α)-dependent pathways activation, and mitochondrial biogenesis, among others. Although polyphenols such as quercetin, catechins, chrysin, luteolin, curcumin, resveratrol, gallic acid, and lignans have shown a positive effect on Non-Shivering Thermogenesis and WAT browning, most of them have only been active in murine models or in vitro systems, and their reproducibility in humans has to be proved. Probably in the future, an approach that includes these compounds as part of the nutritional regimen in conjunction with physical exercise, pharmacological and surgical therapy, would allow modulating a pathophysiological mechanism that is still elusive.