Background Chagas disease (CD) is a major public health concern in Latin America and a potentially serious emerging threat in non-endemic countries. Although the association between CD and cardiac abnormalities is widely reported, study design diversity, sample size and quality challenge the information, calling for its update and synthesis, which would be very useful and relevant for physicians in non-endemic countries where health care implications of CD are real and neglected. We performed to systematically review and meta-analyze population-based studies that compared prevalence of overall and specific ECG abnormalities between CD and non-CD participants in the general population. Methods Six databases (EMBASE, Ovid Medline, Web of Science, Cochrane Central, Google Scholar and Lilacs) were searched systematically. Observational studies were included. Odds ratios (OR) were computed using random-effects model. Results Forty-nine studies were selected, including 34,023(12,276 CD and 21,747 non-CD). Prevalence of overall ECG abnormalities was higher in participants with CD (40.1%; 95%CIs=39.2-41.0) compared to non-CD (24.1%; 95%CIs=23.5-24.7) (OR=2.78; 95%CIs=2.37-3.26). Among specific ECG abnormalities, prevalence of complete right bundle branch block (RBBB) (OR=4.60; 95%CIs=2.97-7.11), left anterior fascicular block (LAFB) (OR=1.60; 95%CIs=1.21-2.13), combination of complete RBBB/LAFB (OR=3.34; 95%CIs=1.76-6.35), first-degree atrioventricular block (A-V B) (OR=1.71; 95%CIs=1.25-2.33), atrial fibrillation (AF) or flutter (OR=2.11; 95%CIs=1.40-3.19) and ventricular extrasystoles (VE) (OR=1.62; 95%CIs=1.14-2.30) was higher in CD compared to non-CD participants. Conclusions This systematic review and meta-analysis provides an update and synthesis in this field. This research of observational studies indicates a significant excess in prevalence of ECG abnormalities (40.1%) related to T. cruzi infection in the general population from Chagas endemic regions, being the most common ventricular (RBBB and LAFB), and A-V B (first-degree) node conduction abnormalities as well as arrhythmias (AF or flutter and VE). Also, prevalence of ECG alterations in children was similar to that in adults and suggests earlier onset of cardiac disease.

BackgroundHBsAg immune-escape mutations can favor HBV-transmission also in vaccinated individuals, promote immunosuppression-driven HBV-reactivation, and increase fitness of drug-resistant strains. Stop-codons can enhance HBV oncogenic-properties. Furthermore, as a consequence of the overlapping structure of HBV genome, some immune-escape mutations or stop-codons in HBsAg can derive from drug-resistance mutations in RT. This study is aimed at gaining insight in prevalence and characteristics of immune-associated escape mutations, and stop-codons in HBsAg in chronically HBV-infected patients experiencing nucleos(t)ide analogues (NA) in Europe.MethodsThis study analyzed 828 chronically HBV-infected European patients exposed to ≥ 1 NA, with detectable HBV-DNA and with an available HBsAg-sequence.The immune-associated escape mutations and the NA-induced immune-escape mutations sI195M, sI196S, and sE164D (resulting from drug-resistance mutation rtM204 V, rtM204I, and rtV173L) were retrieved from literature and examined. Mutations were defined as an aminoacid substitution with respect to a genotype A or D reference sequence.ResultsAt least one immune-associated escape mutation was detected in 22.1% of patients with rising temporal-trend. By multivariable-analysis, genotype-D correlated with higher selection of ≥ 1 immune-associated escape mutation (OR[95%CI]:2.20[1.32–3.67], P = 0.002). In genotype-D, the presence of ≥ 1 immune-associated escape mutations was significantly higher in drug-exposed patients with drug-resistant strains than with wild-type virus (29.5% vs 20.3% P = 0.012). Result confirmed by analysing drug-naïve patients (29.5% vs 21.2%, P = 0.032). Strong correlation was observed between sP120T and rtM204I/V (P < 0.001), and their co-presence determined an increased HBV-DNA.At least one NA-induced immune-escape mutation occurred in 28.6% of patients, and their selection correlated with genotype-A (OR[95%CI]:2.03[1.32–3.10],P = 0.001).Finally, stop-codons are present in 8.4% of patients also at HBsAg-positions 172 and 182, described to enhance viral oncogenic-properties.ConclusionsImmune-escape mutations and stop-codons develop in a large fraction of NA-exposed patients from Europe. This may represent a potential threat for horizontal and vertical HBV transmission also to vaccinated persons, and fuel drug-resistance emergence.

Summary Introduction Caries and orthodontic anomalies in school-age children lead to disturbed aesthetics, oral functions (chewing, swallowing, and speech), predisposition to trauma and the onset of periodontal diseases. The aim was to assess dental health and frequency of orthodontic anomalies in children aged 8-9 years in the municipality of Foča. Methods The research was conducted in the primary school Sveti Sava in Foča, where the total of 112 children age 8-9 years were examined. An informed consent was obtained from parents and school director for each student. Dental examination was performed using standard dental method, a mirror and a probe under artificial lighting. Children received instructions on proper nutrition, oral hygiene, tooth protection and elimination of bad habits. Results Among 112 examined boys and girls of selected ages, very high person caries index (PCI) was found (78.57%). A total of 548 caries affected teeth were found (boys 331 (24.62%), girls 217 (16.14%) (p <0.05)). Fifty-nine children had caries lesions on permanent teeth (boys 39 (2.9%), girls 20 (1.5%) (p <0.05)). Sagital abnormalities of the bite were present in 39 (34.82%) children, while 38 (33.92%) anomalies were related to vertical bite irregularities, 10 (8.92%) of them had open bite and 28 subjects (25%) had deep bite (p> 0.05). Conclusion Large number of teeth was affected with caries lesions (548) in eighth-year-olds, while orthodontic anomalies, mostly sagital abnormalities of bite were found in 39 subjects.

The pathogenesis, clinical course, and response to treatment in systemic juvenile idiopathic arthritis (SJIA) differ from other types of juvenile idiopathic arthritis and are similar to other interleukin-1 (IL-1)-mediated diseases. The main cytokine involved in the pathogenesis of SJIA is IL-1β, which can be neutralized by targeted anti-IL-1 therapy. In SJIA, no antibodies have been found and there is growing evidence that it is mainly an autoinflammatory and not an autoimmune disease. Before the era of biologic therapy, treatment of SJIA was primarily based on long-term treatment with high doses of glucocorticosteroids (GCS). The side effects of GCS could have a significant impact on the outcome of the disease and could cause long-term damage. Treatment with anti-IL-1 agents early in the disease course has revolutionized the management principles of SJIA. However, not all SJIA patients respond equally well to anti-IL-1 therapy, and it has been shown that age at the onset of disease, duration of the disease, number of affected joints, neutrophil count, and ferritin level can predict the response to anti-IL-1 therapy. In particular, an elevated ferritin level should prompt testing for macrophage activation syndrome (MAS), the most severe complication of SJIA. Anti-IL-1 therapy has been shown to be effective also in patients with MAS. Although anti-IL-1 agents are currently not recommended as first-line treatment, there is growing evidence that anti-IL-1 agents introduced at the beginning of SJIA could enable lower doses and a shorter duration of GCS therapy, change the long-term disease outcome, and even influence molecular disease patterns. There are currently three anti-IL-1 agents available: anakinra, canakinumab, and rilonacept. In this review, we present the current knowledge on the pathogenesis of SJIA, the rational for anti-IL-1 treatment, and future perspectives on the treatment of SJIA.

Background Juvenile systemic scleroderma (jSSc) is an orphan disease, with an estimated prevalence of 3 per 1000 000 children. Most jSSc patients primarily present with Raynaud phenomenon (RP). We investigated in our patient of the juvenile scleroderma inception cohort, how fare patients with (RP+) and without (RP-) RP differed in their clinical presentation at enrolment. Methods The jSSc is a prospective cohort of jSSc patients. Patients were enrolled who were diagnosed with jSSc, had a jSSc onset age under 16 years and were younger as age of 18 years at the time of inclusion. The patients are prospectively assessed every 6 months according to a standardised protocol. We reviewed the organ involvement pattern of our patients currently followed in the cohort. Results 100 patients are currently followed in the cohort and 89 (89%) of them had RP. The female/male ratio was lower in the RP +group, 3.7:1 compared to 4.5:1(p=0.808). Diffuse subtype was more common in the RP +group, 72% compared to 63%. Mean age of onset of first non- Raynaud symptomatic was 10.4 years in both groups. Mean disease duration was slightly higher in the RP +group, 3.4 compared to 2.2 years. ANA positivity was higher in the RP +group, 88% compared to 70% (p=0.48). Anti-Scl70 was 34% in the RP +and 20% in the RP-group (p=0.34). Interestingly 7% of RP +but none of the RP +were anti-centromere positive. The mean modified skin score was lower in RP +group (mean of 14.8 compared to 17.0). There were significantly more nailfold capillary changes (70% compared to 18%, p=0.001) and a higher rate of history of ulceration in the RP +group (49% compared to 20%, p=0.083). Decreased DLCO and FVC <80% was higher in the RP-negative group with 45%/50% compared to 37.5%/31% respectively. Pulmonary hypertension occurred in 7% in the RP +group and there was no case in the RP- group (p=0.335). RP- group had a higher rate of urinary sediment changes 18% compared to 4.5% in the RP +group (p=0.07). No renal crisis or hypertension was reported in neither groups. Gastrointestinal involvement was similar between the two groups with around 35%. Occurrence of swollen joints was similar in both groups as the frequency of muscle weakness with around 20%. The tendon friction rub occurred around 10% in both groups. In the patient related outcomes, there was only a difference in rating of Raynauds activity. Conclusions The RP– group differed from RP +group in the clinical presentation at enrolment. The absence of Raynaud phenomenon was associated with a decreased rate of history of ulceration, no occurrence of pulmonary hypertension. Interestingly higher rate of urinary sedimentary changes and no anticentromere positivity was observed in RP- patients. Disclosure of Interest None declared

In this paper, we investigate pilot allocation problem in two-tier time division duplex (TDD) heterogeneous network (HetNet) with mMIMO. First, we propose a new pilot allocation scheme to maximize ergodic downlink sum rate of macro users (MUs) and small cell users (SUs), where the uplink pilot overhead and cross-tier interference are jointly considered. Then, we theoretically analyze the formulated problem and propose a low complexity one-dimensional search algorithm to obtain the optimum pilot allocation. In addition, we propose two suboptimal pilot allocation algorithms to simplify the computational process and improve SUs' fairness, respectively. Finally, simulation results show that the performance of the proposed scheme outperforms that of the traditional schemes.

The IEEE 1901 powerline standard can be deployed using orthogonal frequency division multiplexing (OFDM) since it is robust over impulsive channels. However, the powerline channel picks up impulsive interference that the conventional OFDM driver cannot combat. Since the probability density function (PDF) of OFDM amplitudes follow the Rayleigh distribution, it becomes difficult to correctly predict the existence of impulsive noise (IN) in powerline systems. In this study, we use companding transforms to convert the PDF of the conventional OFDM system to a uniform distribution which avails the identification and mitigation of IN. Results show significant improvement in the output signal-to-noise ratio (SNR) when nonlinear optimization search is applied. We also show that the conventional PDF leads to false IN detection which diminishes the output SNR when nonlinear memoryless mitigation scheme such as clipping or blanking is applied. Thus, companding OFDM signals before transmission helps to correctly predict the optimal blanking or clipping threshold which in turn improves the output SNR performance.

As the age of the Internet of Things (IoT) continues to flourish, the concept of smart healthcare has taken an unprecedented turn due to interdisciplinary thrusts. To carry the big healthcare data ema nating from the plethora of bi 0-sens ors and machines in the IoT sensing plane to the central cloud, next generation high-speed delivery networks are essential. On the other hand, once the IoT data are delivered to the cloud, the massive IoT healthcare data are processed and analyzed em-ploying the state-of-the-art analytics tools such as deep machine learning and so forth. However, given the explosion of big data (from various sources in addition to the healthcare data), the delivery network as well the cloud may experience network and computational congestion, respectively. This may impact the realtime analytics of the healthcare data, e.g., critical for in-house patients and senior citizens aging at home. To address this issue, the emerging IoT edge analytics concept can be regarded as a promising solution to process the big healthcare data close to the source. For larg e-s cale IoT dep loym ents, this fu nctio nality is critical because of the sheer volumes of Data being generated. In this paper, we propose a deep learning based IoT edge analytics approach to support intelligent healthcare for residential users. The performance of the proposal is validated using computer-based simulation for online training of a real dataset. The reported results of our proposal exhibit encouraging performance in terms of low loss rate, high accuracy, and low execution time to support near real-time actionable decision making on the healthcare data.

Seismic properties and equation-of-state parameters of the liquid iron alloy in the outer core are inferred from normal mode data. Turbulent convection of the liquid iron alloy outer core generates Earth’s magnetic field and supplies heat to the mantle. The exact composition of the iron alloy is fundamentally linked to the processes powering the convection and can be constrained by its seismic properties. Discrepancies between seismic models determined using body waves and normal modes show that these properties are not yet fully agreed upon. In addition, technical challenges in experimentally measuring the equation-of-state (EoS) parameters of liquid iron alloys at high pressures and temperatures further complicate compositional inferences. We directly infer EoS parameters describing Earth’s outer core from normal mode center frequency observations and present the resulting Elastic Parameters of the Outer Core (EPOC) seismic model. Unlike alternative seismic models, ours requires only three parameters and guarantees physically realistic behavior with increasing pressure for a well-mixed homogeneous material along an isentrope, consistent with the outer core’s condition. We show that EPOC predicts available normal mode frequencies better than the Preliminary Reference Earth Model (PREM) while also being more consistent with body wave–derived models, eliminating a long-standing discrepancy. The velocity at the top of the outer core is lower, and increases with depth more steeply, in EPOC than in PREM, while the density in EPOC is higher than that in PREM across the outer core. The steeper profiles and higher density imply that the outer core comprises a lighter but more compressible alloy than that inferred for PREM. Furthermore, EPOC’s steeper velocity gradient explains differential SmKS body wave travel times better than previous one-dimensional global models, without requiring an anomalously slow ~90- to 450-km-thick layer at the top of the outer core.

To utilize cervical auscultation as a means of screening for risk of dysphagia, we must first determine how the signal differs between healthy subjects and subjects with swallowing disorders. In this experiment we gathered swallowing sound and vibration data from 53 (13 with stroke, 40 without) patients referred for imaging evaluation of swallowing function with videofluoroscopy. The analysis was limited to non-aspirating swallows of liquid with either thin (< 5 cps) or viscous (≈300cps\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\approx 300\,{\text{cps}}$$\end{document}) consistency. After calculating a selection of generalized time, frequency, and time frequency features for each swallow, we compared our data against our findings in a previous experiment that investigated identical features for a different group of 56 healthy subjects. We found that nearly all of our chosen features for both vibrations and sounds showed significant differences between the healthy and disordered swallows despite the absence of aspiration. We also found only negligible differences between dysphagia as a symptom of stroke and dysphagia as a symptom of another condition. Non-aspirating swallows from healthy controls and patients with dysphagia have distinct feature patterns. These findings should greatly help the development of the cervical auscultation field and serve as a reference for future investigations into more specialized characterization methods.

BackgroundTo utilize cervical auscultation as a means of screening for risk of dysphagia, we must first determine how the signal differs between healthy subjects and subjects with swallowing disorders.MethodsIn this experiment we gathered swallowing sound and vibration data from 53 (13 with stroke, 40 without) patients referred for imaging evaluation of swallowing function with videofluoroscopy. The analysis was limited to non-aspirating swallows of liquid with either thin (< 5 cps) or viscous ($$\approx 300\,{\text{cps}}$$≈300cps) consistency. After calculating a selection of generalized time, frequency, and time frequency features for each swallow, we compared our data against our findings in a previous experiment that investigated identical features for a different group of 56 healthy subjects.ResultsWe found that nearly all of our chosen features for both vibrations and sounds showed significant differences between the healthy and disordered swallows despite the absence of aspiration. We also found only negligible differences between dysphagia as a symptom of stroke and dysphagia as a symptom of another condition.ConclusionNon-aspirating swallows from healthy controls and patients with dysphagia have distinct feature patterns. These findings should greatly help the development of the cervical auscultation field and serve as a reference for future investigations into more specialized characterization methods.

The increasing energy demands of modern society require a deep understanding of the properties of energy storage materials, as well as the tuning of their performance. We show that the capacitance of graphene oxide (GO) can be precisely tuned using a simple electrochemical reduction route. In situ resistance measurements, in combination with cyclic voltammetry measurements and Raman spectroscopy, have shown that upon reduction GO is irreversibly deoxygenated, which is further accompanied by structural ordering and an increase in electrical conductivity. The capacitance is maximized when the concentration of oxygen functional groups is properly balanced with the conductivity. Any further reduction and deoxygenation leads to a gradual loss of capacitance. The observed trend is independent of the preparation route and the exact chemical and structural properties of GO. It is proposed that an improvement in the capacitive properties of any GO can be achieved by optimization of its reduction conditions.