Diffusion magnetic resonance imaging is a noninvasive imaging modality that has been extensively used in the literature to study the neuronal architecture of the brain in a wide range of neurological conditions using tractography. However, recent studies highlighted that the anatomical accuracy of the reconstructions is inherently limited and challenged its appropriateness. Several solutions have been proposed to tackle this issue, but none of them proved effective to overcome this fundamental limitation. In this work, we present a novel processing framework to inject into the reconstruction problem basic prior knowledge about brain anatomy and its organization and evaluate its effectiveness using both simulated and real human brain data. Our results indicate that our proposed method dramatically increases the accuracy of the estimated brain networks and, thus, represents a major step forward for the study of connectivity.

INTRODUCTION: Gastrointestinal symptoms in irritable bowel syndrome (IBS) have been correlated with psychological factors using retrospective symptom assessment. However, real-time symptom assessment might reveal the interplay between abdominal and affective symptoms more reliably in a longitudinal perspective. The aim was to evaluate the association between stress and abdominal pain, using the Experience Sampling Method (ESM) as a real-time, repeated measurement method. METHODS: Thirty-seven patients with IBS (26 women; mean age 36.7 years) and 36 healthy controls (HC; 24 women; mean age 31.1 years) completed an electronic ESM during 7 consecutive days. Abdominal pain and stress were scored on an 11-point Numeric Rating Scale at a maximum of 10 random moments each day. RESULTS: Abdominal pain scores were 2.21 points higher in patients with IBS compared with those in HC (P < 0.001), whereas stress levels did not differ significantly (B: 0.250, P = 0.406). In IBS, a 1-point increase in stress was associated with, on average, 0.10 points increase in abdominal pain (P = 0.017). In HC, this was only 0.02 (P = 0.002). Stress levels at t = −1 were not a significant predictor for abdominal pain at t = 0 in both groups, and vice versa. DISCUSSION: Our results demonstrate a positive association between real-time stress and abdominal pain scores and indicate a difference in response to stress and not a difference in experienced stress per se. Furthermore, an in-the-moment rather than a longitudinal association is suggested. This study underlines the importance of considering the individual flow of daily life and supports the use of real-time measurement when interpreting potential influencers of abdominal symptoms in IBS.

Lung sound (LS) signals are often contaminated by impulsive artifacts that complicate the estimation of lung sound intensity (LSI) using conventional amplitude estimators. Fixed sample entropy (fSampEn) has proven to be robust to cardiac artifacts in myographic respiratory signals. Similarly, fSampEn is expected to be robust to artifacts in LS signals, thus providing accurate LSI estimates. However, the choice of fSampEn parameters depends on the application and fSampEn has not previously been applied to LS signals. This study aimed to perform an evaluation of the performance of the most relevant fSampEn parameters on LS signals, and to propose optimal fSampEn parameters for LSI estimation. Different combinations of fSampEn parameters were analyzed in LS signals recorded in a heterogeneous population of healthy subjects and chronic obstructive pulmonary disease patients during loaded breathing. The performance of fSampEn was assessed by means of its cross-covariance with flow signals, and optimal fSampEn parameters for LSI estimation were proposed.

Cardiovascular disease (CVD) is the biggest cause of sickness and mortality worldwide in both males and females. Clinical statistics demonstrate clear sex differences in risk, prevalence, mortality rates, and response to treatment for different entities of CVD. The reason for this remains poorly understood. Non-coding RNAs (ncRNAs) are emerging as key mediators and biomarkers of CVD. Similarly, current knowledge on differential regulation, expression, and pathology-associated function of ncRNAs between sexes is minimal. Here, we provide a state-of-the-art overview of what is known on sex differences in ncRNA research in CVD as well as discussing the contributing biological factors to this sex dimorphism including genetic and epigenetic factors and sex hormone regulation of transcription. We then focus on the experimental models of CVD and their use in translational ncRNA research in the cardiovascular field. In particular, we want to highlight the importance of considering sex of the cellular and pre-clinical models in clinical studies in ncRNA research and to carefully consider the appropriate experimental models most applicable to human patient populations. Moreover, we aim to identify sex-specific targets for treatment and diagnosis for the biggest socioeconomic health problem globally.

Long QT syndrome (LQTS) is a rare (1:2500–1:10,000) inherited disorder characterized by the onset of arrhythmogenic syncope, polymorphic ventricular tachycardia, and sudden cardiac death. The aim of this article was to describe an unexpected success with an unusual therapeutic modality of a patient diagnosed with LQTS syndrome (suspected Romano–Ward syndrome) during an 8-year period. A 59-year-old female patient was admitted to the hospital due to chest pain and nausea, and after diagnostic and therapeutical approach, a permanent dual-chamber rate-modulated (DDDR) pacemaker was implanted instead of the implantable cardioverter defibrillator (ICD). During the 8-year period, the patient remained stable, without rhythm disorder. Romano–Ward syndrome as a congenital LQTS carries a high risk of sudden cardiac death and presents an indication for ICD. In this patient, for objective reasons, this could not be performed. Implantation of a DDDR with an appropriate pharmacological therapy, including propranolol, in this case, proved to be a successful therapeutic modality.

Introduction: The head-up tilt table test is noninvasive diagnostic procedure, which is used in the diagnosis of syncope. Syncope presents a benign short-term disorder of cerebral circulation with the sudden loss of consciousness and muscle tone. Aim: The aim is to present not only the role and importance of orthostatic tests in the daily clinical practice of pediatric cardiology, neuropediatrics but also pediatrics in general. Patients and Methods: This study has retrospective descriptive character and included the period from April 1997 to June 2020, during which the registration and analysis of orthostatic stability tests (head-up/tilt table test, tilt table test) was performed. Medical documentation of outpatient and hospitalized patients on the Paediatric Clinic of Clinical Center University of Sarajevo (Register of Tilt Table Test) was used. Results: During this period, 1029 tests were registered and analyzed. Modification test (head-up) was performed in 132 (12.8%) patients, and since 2008, classic tilt table test was performed in 897 (87.1%) patients. Patients were 6.5–19 years old, with a predominance of female patients 611 (59.4%). There were 519 (50.4%) patients who were 15–19 years old and 510 (49.6%) patients who were under 15 years of age. Indications were syncope or suspected syncope in 671 (65.2%) patients, cardiovascular etiology (arrhythmias, chest pain, congenital heart defects [CHDs], surgically corrected CHDs, hypotension, and hypertension) in 195 (19%) patients, neuropediatric pathology (epilepsia, suspected epilepsia, headache, vertigo) in 101 (9.8%) patients, and other indications in 62 (6.03%) patients. From the total number of tests, 862 were first tests (83.4%) and 167 were control tests (16.3%). The positive test was found in 538 (52.3%) patients, most often vasovagal syncope (473 patients or 87.9%). Conclusion: Tilt table test is a reliable diagnostic tool in examining the etiology of syncope, primarily vasovagal, and is an extremely important method primarily in cardiopediatric and neuropediatric daily diagnostics.

We present a real-time feasible Nonlinear Model Predictive Control (NMPC) scheme to control a microgrid described by a detailed Differential Algebraic Equation (DAE). Our NMPC formulation allows to consider secondary voltage and frequency control, steady-state equal load sharing, economic goals and all relevant operational constraints in a single optimization problem. The challenge is to control the fast and large dynamical system in real-time. To achieve this goal, we use the recently introduced Advanced Step Real-Time Iteration (AS-RTI) scheme and its efficient implementation in the acados software package. We present an NMPC scheme which delivers feedback in the range of milliseconds. Thereby, the controller responds efficiently to large disturbances and mismatches in the predictions and effectively controls the fast transient dynamics of the microgrid. Our NMPC approach outperforms a state-of-the-art I-controller usually used in microgrid control and shows minor deviation to a fully converged NMPC approach.

The network edge presses an urgent need for efficient network management and orchestration (MANO), in order to efficiently cope with the wide heterogeneity in services and resources, while providing a low-latency for the hosted services. Based on ETSI standardization, the MEC platform can be managed and orchestrated by NFV MANO components. In this demo, we show how to measure the impact of the Virtualized Infrastructure Manager (VIM), which is a component of the NFV MANO, on the performance of the MANO system. In our testbed-based experimentation, we evaluated the performance in terms of time needed for a MANO system to instantiate/terminate a network service on top of the MEC platform. Open Source MANO (OSM) and Open Baton are used as MANO entities, while for the VIM environments we investigated the impact of OpenStack and Amazon Web Services (AWS) on the above-mentioned OSM, and the impact of OpenStack and Docker on Open Baton.

By providing storage and computational resources at the network edge, which enables hosting applications closer to the mobile users, Multi-Access Edge Computing (MEC) uses the mobile backhaul, and the network core more efficiently, thereby reducing the overall latency. Fostering the synergy between 5G and MEC brings ultra-reliable low-latency in data transmission, and paves the way towards numerous latency-sensitive automotive use cases, with the ultimate goal of enabling autonomous driving. Despite the benefits of significant latency reduction, bringing MEC platforms into 5G-based vehicular networks imposes severe challenges towards poorly scalable network management, as MEC platforms usually represent a highly heterogeneous environment. Therefore, there is a strong need to perform network management and orchestration in an automated way, which, being supported by Software Defined Networking (SDN) and Network Function Virtualization (NFV), will further decrease the latency. With recent advances in SDN, along with NFV, which aim to facilitate management automation for tackling delay issues in vehicular communications, we study the closed-loop life-cycle management of network services, and map such cycle to the Management and Orchestration (MANO) systems, such as ETSI NFV MANO. In this paper, we provide a comprehensive overview of existing MANO solutions, studying their most important features to enable network service and resource orchestration in MEC-enhanced vehicular networks. Finally, using a real testbed setup, we conduct and present an extensive performance analysis of Open Baton and Open Source MANO that are, due to their lightweight resource footprint, and compliance to ETSI standards, suitable solutions for resource and service management and orchestration within the network edge.

Background Immune-related diarrhoea/colitis (ir-D/C) is a common adverse event of immune checkpoint inhibitor (ICI) therapy. Guidelines recommend corticosteroid (CS) treatment; however, the average treatment duration for ir-D/C remains poorly defined. Methods All advanced melanoma patients treated with ICI therapy at the Royal Marsden Hospital between 2011 and 2016 were reviewed to identify ir-D/C cases alongside clinical variables. Results 117 any-grade ir-D/C episodes occurred in 109 (21%) patients out of a total of 519 patients treated (ipilimumab=77 episodes, anti-PD1=17 (nivolumab or pembrolizumab), ipilimumab and nivolumab=23 (ipi+nivo)) (seven patients had ir-D/C more than once on different lines of treatment) and >/=grade 3 ir-D/C occurred most frequently (63/519 patients (12%) vs 29/519 (5%) grade 1, and 25/519 (5%) grade 2). Median onset (days) of all-grade ir-D/C after starting ICI therapy was 41 for ipilimumab (IQR 24 to 59, n=77), 91 for anti-PD1 (IQR 46 to 355, n=17) and 45 for ipi+nivo (IQR 24 to 67, n=23). In 71/117 (61%) patients, ir-D/C episodes were treated with CS (17% grade 2; 79% grade 3/4): 54 being steroid-responsive; 17 being steroid-refractory and received additional anti-tumor necrosis factor (TNF) treatment. Median grade 3 ir-D/C CS duration was similar across treatments, averaging 58 days. Median overall CS duration (days) was longer in the grade 3/4 D/C steroid-refractory group (94 vs 45 days). Infection developed in 11/71 (15%) CS recipients and in 6/17 (35%) anti-TNF recipients. In 65/117 (55%) patients, ir-D/C episodes were investigated with flexible sigmoidoscopy. Of these patients, 38/65 (58%) had macroscopic colitis and 12/65 (18%) had microscopic colitis. The steroid-refractory group had more macroscopic changes, 13/17 (76%), than the steroid-responsive group, 22/41 (54%). Conclusion Rates of grade 3 ir-D/C were higher than reported in clinical trials. The 58-day median duration of CS therapy for grade 3 ir-D/C places a significant number of patients at risk of complications. We demonstrate that microscopic colitis is an important subgroup, advocating biopsies in ir-D/C even with macroscopically normal bowel.