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Summary Background Patients with COVID-19 pneumonia can have increased inflammation and elevated cytokines, including interleukin (IL)-6, which might be deleterious. Thus, sarilumab, a high-affinity anti-IL-6 receptor antibody, might improve the outcome of patients with moderate-to-severe COVID-19 pneumonia. Methods We did a multicentric, open-label, Bayesian randomised, adaptive, phase 2/3 clinical trial, nested within the CORIMUNO-19 cohort, to test a superiority hypothesis. Patients 18 years or older hospitalised with COVID-19 in six French centres, requiring at least 3L/min of oxygen but without ventilation assistance and a WHO Clinical Progression Scale [CPS] score of 5 were enrolled. Patients were randomly assigned (1:1) via a web-based system, according to a randomisation list stratified on centre and with blocks randomly selected among 2 and 4, to receive usual care plus 400 mg of sarilumab intravenously on day 1 and on day 3 if clinically indicated (sarilumab group) or usual care alone (usual care group). Primary outcomes were the proportion of patients with WHO-CPS scores greater than 5 on the 10-point scale on day 4 and survival without invasive or non-invasive ventilation at day 14. This completed trial is closed to new participants and is registered with ClinicalTrials.gov , NCT04324073 . Findings 165 patients were recruited from March 27 to April 6, 2020, and 148 patients were randomised (68 patients to the sarilumab group and 80 to the usual care group) and followed up for 90 days. Median age was 61·7 years [IQR 53·0–71·1] in the sarilumab group and 62·8 years [56·0–71·7] in the usual care group. In the sarilumab group 49 (72%) of 68 were men and in the usual care group 59 (78%) of 76 were men. Four patients in the usual care group withdrew consent and were not analysed. 18 (26%) of 68 patients in the sarilumab group had a WHO-CPS score greater than 5 at day 4 versus 20 (26%) of 76 in the usual care group (median posterior absolute risk difference 0·2%; 90% credible interval [CrI] −11·7 to 12·2), with a posterior probability of absolute risk difference greater than 0 of 48·9%. At day 14, 25 (37%) patients in the sarilumab and 26 (34%) patients in the usual care group needed ventilation or died, (median posterior hazard ratio [HR] 1·10; 90% CrI 0·69–1·74) with a posterior probability HR greater than 1 of 37·4%. Serious adverse events occurred in 27 (40%) patients in the sarilumab group and 28 (37%) patients in the usual care group (p=0·73). Interpretation Sarilumab treatment did not improve early outcomes in patients with moderate-to-severe COVID-19 pneumonia. Further studies are warranted to evaluate the effect of sarilumab on long-term survival. Funding Assistance publique—Hopitaux de Paris

This article examines the poetry of Andrei Ciurunga (1920-2002), the pseudonym of Robert Esenbraun, born in a family of German settlers in southern Bessarabia. Under the communist regime he was sentenced on two occasions (the first time to four years, 19501954, the second time to 18 years to prison – from 1958), he was detained for a little more than ten years, undergoing amnesty in 1964. Memorable is the poem published after the fall of communism. It is a poem „coming from the heart”. The author has identified his destiny with the poetry of detention in all prisons and jails of Romania (Gherla, Salcia, Jilava, Văcărești, Peninsula, Poarta Albă, Danube - Black Sea canal). The lyrics "From the Canal" are distinguished by the invention of a new fixed form of poetry, the decastih. They were mentally composed and circulated widely among the detainees. It reveals, retroactively, another world, a world from the carceral inferno.

Mesenchymal stromal cells (MSC) are nonhematopoietic cells with fibroblast-like morphology and multipotent capacity that are widely used in pre-clinical and clinical investigations. Unfortunately, the efficiency of MSC treatment is hindered by the poor survival rate after transplantation at the damaged tissue. The goal of this study was to investigate the fate of MSC exposed to various stimuli mimicking the in vivo microenvironment post transplantation. To this aim, murine bone marrow–derived MSC were stimulated with IFNγ and TNFα under low oxygen (hypoxia) or atmospheric (normoxia) conditions for 24 to 72 hours, in order to better mimic an ischemic injury. The results showed that MSC pre-stimulation with TNFα and IFNγ enhanced immunosuppressive pathways by over-expression of NOS2, IDO, COX2 and production of NO. However, MSC viability was affected by these two cytokines in dose-dependent and time-dependent manners. Besides, priming with TNFα and/or IFNγ under low oxygen concentrations revealed that significantly increased cell mortality rate and decreased NO production. Our data suggest that both hypoxia and inflammation could impact the cell survival after transplantation and reinforces the necessity of further investigations to better understand MSC behavior after transplantation in order to identify the MSC-based strategies with the highest therapeutic potential.

Currently, an impressive number of patients have been diagnosed with atrial fibrillation (AF) receiving a reliable indication for oral anticoagulation therapy (OAT) either with vitamin K inhibitors...

Background Colonoscopy with biopsy is the "gold" standard for evaluating disease activity in inflammatory bowel diseases (IBD). Current research is geared toward finding non-invasive, cost-efficient methods that estimate disease activity. We aimed to develop a neural network (NN) model for the non-invasive prediction of histologic activity in IBD using routinely available clinical-biological parameters. Methods Standard clinical-biological parameters and histologic activity from 371 ulcerative colitis (UC) and 115 Crohn's disease (CD) patient records were collected. A training set, a test set, and a validation set were used for building/validating 2 models for each disease. All models had binary output predicting the active/inactive histologic disease status. For both diseases, the first model used both clinical and biological inputs, while the second used only biological data. Results First UC model obtained an accuracy of 95.59% on the test set and 96.67% on the validation set. The second UC model achieved accuracies of 88.24% and 86.67% on the test and validation sets, respectively. The First CD classifier resulted in 90.48% accuracy on the test set and 91.67% on the validation set. Finally, the second CD classifier obtained an accuracy of 85.71% on the test set and 91.67% on the validation set. Conclusions An accurate and non-invasive artificial intelligence system to predict histologic disease activity in IBD is designed. Our models achieved similar or better results compared to the documented performance of fecal calprotectin (the best non-invasive IBD biomarker to date). Given these favorable results, we anticipate the future utility in the clinical setting of a non-invasive disease activity prediction.

Imposing “sin” taxes has been the preferred way governments tried to discourage the over-consumption of temptation goods for decades. However numerous evidence shows that consumers exhibit behavioral biases which can affect their reaction to taxes. This paper investigates a potential bias and how it affects demand for temptation: financial worries associated with poverty have been shown to shift attention towards pressing needs, often at the expense of forward-looking decisions. In an online experiment with UK participants, we randomly induce financial worries and ask participants to allocate a budget between basic necessities and temptation goods in an experimental market. We randomly impose “taxes” on temptation by increasing its price. We find that, in the absence of any tax, inducing financial worries lowers demand for temptation, effect stronger for lower-income participants. However, when financial concerns are salient, increasing the tax does not lower demand among lower-income participants. While financial worries might protect against over-consumption of temptation in the absence of tax changes, they also might hurt the poor the most when additional taxes are introduced.

The melanoma, having its origin in the melanocyte cells, is one of the most aggressive forms of skin cancer in the world with one of the highest rates of brain metastasis. The incidence of cutaneous melanoma in the Mediterranean countries varies from three to five cases∕100 000 people∕year. Its prognosis is based on an early diagnosis. Sinonasal mucosal melanoma (SNMM) is an extremely rare tumor, accounting for 0.3-2% of all melanomas. The non-specific symptomatology is often delaying the presentation of the patient at the hospital and therefore the diagnosis. The SNMM is a highly aggressive tumor, and the presence of metastasis at the diagnosis usually implies a poor prognosis. The management of the melanomas requires a precise pre-therapeutic assessment and a multidisciplinary approach for the diagnosis, with surgical treatment or radiotherapy required in order to ensure a better a quality of life. In this paper, we retrospectively analyzed two cases of mucosal melanoma and one case of cutaneous melanoma of the nose.

Background A high prevalence of pulmonary embolism (PE) has been described during COVID‐19. Our aim was to identify predictive factors of PE in non‐ICU hospitalized COVID‐19 patients. Methods Data and outcomes were collected upon admission during a French multicenter retrospective study, including patients hospitalized for COVID‐19, with a CT pulmonary angiography (CTPA) performed in the emergency department for suspected PE. Predictive factors significantly associated with PE were identified through a multivariate regression model. Results A total of 88 patients (median [IQR] age of 68 years [60‐78]) were analyzed. Based on CTPA, 47 (53.4%) patients were diagnosed with PE, and 41 were not. D‐dimer ≥3000 ng/mL (OR 8.2 [95% CI] 1.3‐74.2, sensitivity (Se) 0.84, specificity (Sp) 0.78, P = .03), white blood count (WBC) ≥12.0 G/L (29.5 [2.3‐1221.2], Se 0.47, Sp 0.92, P = .02), and ferritin ≥480 µg/L (17.0 [1.7‐553.3], Se 0.96, Sp 0.44, P = .03) were independently associated with the PE diagnosis. The presence of the double criterion D‐dimer ≥3000 ng/mL and WBC ≥12.0 G/L was greatly associated with PE (OR 21.4 [4.0‐397.9], P = .004). Conclusion The white blood count, the D‐dimer and ferritin levels could be used as an indication for CTPA to confirm PE on admission in non‐ICU COVID‐19 patients.

Colonoscopy is the “gold” standard for evaluating disease activity in ulcerative colitis (UC). An important area of research is finding a cost-efficient, non-invasive solution for estimating disease activity. We aimed to develop and validate a neural network (NN) model that uses routinely available clinical–biological variables to predict UC activity. Standard clinical–biological parameters and endoscopic Mayo score from 386 UC patient records were collected. A training set (n = 285), a test set (n = 71) and a validation set (n=30) were used for constructing and validating three NN models. The first two models predicted the active/inactive endoscopic disease status through a binary output. The third model estimated the complete endoscopic Mayo score through a categorical output. First model (with seven categorical and 13 continuous input variables) obtained an accuracy of 94.37% on the test set and 93.33% on the validation set. The second model (with 12 biological input parameters) achieved an accuracy of 88.73% on the test set and 83.33% on the validation set. The third model used the same input variables as the first model obtaining an accuracy of 76.06% on the test set and 80% on the validation set. We designed an accurate and non-invasive artificial intelligence solution to estimate disease activity, other than colonoscopy. Our NN model achieved better results than pooled performance metrics of fecal calprotectin (the best non-invasive marker to date) investigated in UC. Given these promising results, we envision introducing of a non-invasive algorithm for routinely predicting disease activity shortly.

Background: Interpretation of thyroid function tests by means of biological variation (BV) data is essential to identify significant changes between serial measurements at an individual level. Data on thyroid parameters in adults are limited. Objectives: We aimed at determining the BV of four thyroid function test (thyroid-stimulating hormone (TSH), free thyroxin (FT4), free triiodothyronine (FT3) and thyroglobulin (Tg)) by applying recent recommendations to acquire BV data on a latest generation of immunoassay. Methods: Nineteen healthy volunteers (8 males and 11 females) were drawn every week during 5 consecutive weeks. Samples were analysed in duplicate on the Cobas 602 analyzer (Roche Diagnostics). After normality assessment, outlier exclusion and homogeneity of variance analysis, analytical variation (CVA), within-subject biological variation (CVI) and between-subject biological variation (CVG) were determined using nested ANOVA. Results: CVA, CVI and CVG were 0.9%, 19.7% and 37.6% for TSH; 3.6%, 4.6% and 10.8% for FT4; 2.2%, 6.0% and 8.6% for FT3; and 0.9%, 15.4% and 84.9% for Tg. Index of individuality (II) for all parameters was between 0.2 and 0.7. The percentage above which the change between two measures is truly significant (reference change value) was 54.7% for TSH, 16.2% for FT4, 17.7% for FT3 and 42.8% for Tg. Conclusion: Based on recent international recommendations, our study provides updated BV data for four thyroid function tests in European healthy volunteers. Reliable BV characteristics, and especially RCV, can facilitate the interpretation of consecutive thyroid function tests in an individual and therefore have the potential to efficiently support clinical decisions regarding thyroid diseases.

Purpose The mass electronics sector is one of the most critical sources of waste, in terms of volume and content with dangerous effects on the environment. The purpose of this study is to provide an automated and accurate dismantling system that can improve the outcome of recycling. Design/methodology/approach Following a short introduction, the paper details the implementation layout and highlights the advantages of using a custom architecture for the automated dismantling of printed circuit board waste. Findings Currently, the amount of electronic waste is impressive while manual dismantling is a very common and non-efficient approach. Designing an automatic procedure that can be replicated, is one of the tasks for efficient electronic waste recovery. This paper proposes an automated dismantling system for the advanced recovery of particular waste materials from computer and telecommunications equipment. The automated dismantling architecture is built using a robotic system, a custom device and an eye-to-hand configuration for a stereo vision system. Originality/value The proposed approach is innovative because of its custom device design. The custom device is built using a programmable screwdriver combined with an innovative rotary dismantling tool. The dismantling torque can be tuned empirically.

International audience

During the past decade, welding remained the main technological procedure for joining steel components in shipbuilding industry. Though it has great benefits, welding is an aggressive process that introduces high stress and strains in the joined materials, causing distortion. Finite element method is an important instrument for predicting how structures are behaving under thermal loads. This paper is focused on studying the behaviour of small thickness ship panels, under straightening treatment, by performing thermal-structural-elastic-plastic analysis in Femap/NX Nastran. The proposed panel is tested under three different thermal loadings in order to study stresses and residual distortion.

Dialysis patients manifest both an increased thrombotic risk and a haemorrhagic tendency. A great number of patients with chronic kidney disease requiring dialysis have cardiovascular comorbidities (coronary artery disease, atrial fibrillation or venous thromboembolism) and different indications for treatment with antithrombotics (primary or secondary prevention). Unfortunately, few randomized controlled trials deal with antiplatelet and/or anticoagulant therapy in dialysis. Therefore cardiology and nephrology guidelines offer ambiguous recommendations and often exclude or ignore these patients. In our opinion, there is a need for an expert consensus that provides physicians with useful information to make correct decisions in different situations requiring antithrombotics. Herein the European Dialysis Working Group presents up-to-date evidence about the topic and encourages practitioners to choose among alternatives in order to limit bleeding and minimize atherothrombotic and cardioembolic risks. In the absence of clear evidence, these clinical settings and consequent therapeutic strategies will be discussed by highlighting data from observational studies for and against the use of antiplatelet and anticoagulant drugs alone or in combination. Until new studies shed light on unclear clinical situations, one should keep in mind that the objective of treatment is to minimize thrombotic risk while reducing bleeding events.

The COVID-19 pandemic rapidly became a worldwide healthcare emergency affecting millions of people, with poor outcomes for patients with chronic conditions and enormous pressure on healthcare systems. Pulmonary fibrosis (PF) has been cited as a risk factor for a more severe evolution of COVID-19, primarily because its acute exacerbations are already associated with high mortality. We reviewed the available literature on biochemical, pathophysiological, and pharmacological mechanisms of PF and COVID-19 in an attempt to foresee the particular risk of infection and possible evolution of PF patients if infected with SARS-COV-2. We also analyzed the possible role of medication and risk factors (such as smoking) in the disease’s evolution and clinical course. We found out that there is a complexity of interactions between coexisting idiopathic pulmonary fibrosis/interstitial lung disease (ILD) and COVID-19 disease. Also, patients recovering from severe COVID-19 disease are at serious risk of developing PF. Smokers seem to have, in theory, a chance for a better outcome if they develop a severe form of COVID-19 but statistically are at much higher risk of dying if they become critically ill.

Subcutaneous transplantation of mesenchymal stromal cells (MSC) emerged as an alternative to intravenous administration because it avoids the pulmonary embolism and prolongs post‐transplantation lifetime. The goal of this study was to investigate the mechanisms by which these cells could affect remote organs. To this aim, murine bone marrow–derived MSC were subcutaneously transplanted in different anatomical regions and the survival and behaviour have been followed. The results showed that upon subcutaneous transplantation in mice, MSC formed multicellular aggregates and did not migrate significantly from the site of injection. Our data suggest an important role of hypoxia‐inducible signalling pathways in stimulating local angiogenesis and the ensuing modulation of the kinetics of circulating cytokines with putative protective effects at distant sites. These data expand the current understanding of cell behaviour after subcutaneous transplantation and contribute to the development of a non‐invasive cell‐based therapy for distant organ protection.

This paper examines the corporate governance and sustainability disclosure and investigates the existing anchor between sustainability disclosure and corporate governance in Romanian companies. The topic provides a generous field of study because of the novelty of sustainable reporting for the Romanian companies and need for robust, consolidated corporate governance. The study’s sample includes listed and non-listed companies operating in the oil, transportation, chemistry and pharmaceutical industries. Annual reports, comply-or-explain declarations and stand-alone sustainability reports of the companies were analyzed on a time frame of three years aiming at measure the quality of sustainability disclosures and investigate the correlations between board governance and sustainability disclosure. The study emphasized that the companies opted mainly to integrate sustainable reporting in the annual management report. The independent reports on sustainability are more rigorous and better aligned to the Romanian framework, then the information integrated into the annual management reports. Improved disclosure is needed on the main risks with severe impacts, policies regarding specific aspects of sustainability, key performance indicators relevant to particular businesses. The sustainability reporting is more focus on soft disclosure items. Companies with larger board size and a higher number of board meetings registered higher disclosure in sustainability reporting. Robust corporate governance is imperative for Romanian companies because they are facing drastic changes in all aspects of their activity. A new rethink approach is needed from the sustainability perspective aiming at reshaping the entire processes starting with a long-term strategy, business models, risk and data management and processing.

Background. The purpose of this review is to depict current research and impact of artificial intelligence/machine learning (AI/ML) algorithms on dialysis and kidney transplantation. Published studies were presented from two points of view: What medical aspects were covered? What AI/ML algorithms have been used? Methods. We searched four electronic databases or studies that used AI/ML in hemodialysis (HD), peritoneal dialysis (PD), and kidney transplantation (KT). Sixty-nine studies were split into three categories: AI/ML and HD, PD, and KT, respectively. We identified 43 trials in the first group, 8 in the second, and 18 in the third. Then, studies were classified according to the type of algorithm. Results. AI and HD trials covered: (a) dialysis service management, (b) dialysis procedure, (c) anemia management, (d) hormonal/dietary issues, and (e) arteriovenous fistula assessment. PD studies were divided into (a) peritoneal technique issues, (b) infections, and (c) cardiovascular event prediction. AI in transplantation studies were allocated into (a) management systems (ML used as pretransplant organ-matching tools), (b) predicting graft rejection, (c) tacrolimus therapy modulation, and (d) dietary issues. Conclusions. Although guidelines are reluctant to recommend AI implementation in daily practice, there is plenty of evidence that AI/ML algorithms can predict better than nephrologists: volumes, Kt/V, and hypotension or cardiovascular events during dialysis. Altogether, these trials report a robust impact of AI/ML on quality of life and survival in G5D/T patients. In the coming years, one would probably witness the emergence of AI/ML devices that facilitate the management of dialysis patients, thus increasing the quality of life and survival.

In this issue of Clinical Kidney Journal, Park et al. presents the results of a nationwide population-based trial that included >5000 dialysis patients receiving a drug-eluting stent (DES). The main objective was to evaluate the effectiveness and the safety of prolonged dual antiplatelet therapy (DAPT). The primary outcome was a composite of mortality, non-fatal myocardial infarction, coronary revascularization and stroke, significantly lowered by a longer DAPT regimen at 12, 15 and 18 months, respectively. Longer DAPT tended to be correlated with higher bleeding events at all landmarks, with no statistical significance. An important element was that almost 75% of the index events were acute coronary syndromes. This study presents the first solid evidence for a significant benefit of prolonged DAPT in dialysis patients receiving a DES. We believe that end-stage renal disease is still in the middle of a rope game, being pulled to one side or another by other features, inclining towards a higher bleeding risk or towards higher ischaemic risk. The acute versus elective presentation seems to weigh in choosing the antiplatelet regimen. The ‘one-size-fits-all strategy’ is not suitable for this particular group. Probably in the future, practitioners will be provided with decision pathways generated by artificial intelligence algorithms yielding ‘truly individualized’ DAPT protocols for every single patient.

The present paper proposes to determine the types of organizational cultures that exist within the Romanian textileindustry, starting off from Handy’s typology according to which there are four types of cultures, respectively the TaskTypes, the Power Types, the Role Types and the Person Type. In this sense, we have conducted an empirical studymade up of two questionnaires, the first regarding the organizational culture within the Romanian textile industry – fromthe point of view of employees without leadership positions, and the second regarding the organizational culture withinthe Romanian textile industry – from the managerial point of view. Interviews were conducted on employees andmanagers from local companies, by using direct questions, with multiple choice answers, with the purpose of ensuringtransparency and objectivity when processing and analyzing the data. The database of this study contains 110completed and validated questionnaires, divided into the two respondent categories: employees in leadership positions– 65 questionnaires, operating personnel – 45 questionnaires. By utilizing the Cronbach Alpha test, a correlation matrix,the KMO and Bartlett test, a functional analysis, we have validated the viability, the relevance of the items, the existenceof a correlation between them, the construction of synthetic variables, thus demonstrating the presence of 4 types oforganizational cultures within the Romanian textile industry

This research is presenting a theoretical approach to an innovative icing prevention method. The system is using heat pipes to extract the thermal energy stored in the ground in the hot season, and use it for preventing walkways to freeze during cold seasons, for Romania’s climatic conditions. The method may prove to be very efficient and less expensive than the classic solutions since the heat transfer from the ground to the pavement is passive.

Introduction Marked isolated elevation of cardiac biomarkers (CK-MB, cardiac troponin I, heart-type fatty acid binding protein, hFABP) within 48 hours after coronary artery bypass surgery (CABG), even in the absence of electrocardiographic/angiographic evidence of myocardial infarction (MI), indicates prognostically significant cardiac procedural myocardial injury. There are no data exploring the relationship between the complexity of coronary atherosclerotic burden and early post-CABG myocardial injury. Aim To analyse correlations and predictive strength of the SYNTAX score (SS) for early myocardial injury after on-pump CABG. Material and methods One hundred and twenty consecutive patients undergoing CABG were included in the analysis. We obtained data on demographics, medical history, cardiovascular risk factors and echocardiography. Cardiac biomarkers were assessed at 6 hours after CABG. Multivariate linear regression analysis was performed to evaluate independent variables correlated with cardiac biomarkers. Results The most significant predictor for myocardial injury was SS, strongly correlated with the rise of all cardiac biomarkers (p < 0.001). Hypertension and creatinine clearance were associated with cTnI and hFABP. Diabetes was corelated with hFABP. In a multivariate analysis including all significant predictors, SS remained an independent predictor for myocardial injury, strongly associated with hFABP (p < 0.001, OR = 5.79, 95% CI: 3.59-7.98), cTnI (p < 0.001, OR = 6.49, 95% CI: 4.78-8.20), but not with CK-MB (95% CI: 0.61-1.07). Conclusions Defining myocardial injury as elevation of cardiac biomarkers between normal values and the cut-off for MI has a tremendous clinical significance as patients maintain high negative prognostic rates. SS could be used to predict post-operative rise of cardiac biomarkers, the correlation between SS and myocardial injury being very solid.

The novice anaesthesiology trainee must rapidly assimilate the cognitive, technical and non-technical skills necessary to competently respond to critical events in their new role. Providing trainees with the safe and controlled environment of high-fidelity patient simulation is one method to compensate for gaps in trainee experience, offering the potential for effective training. An anaesthesiology boot camp was set up to increase the knowledge, clinical, technical and non-technical competencies of the novice trainee, creating a framework for their future learning and practice. Anaesthetic nurses also attended to incorporated teamwork and collaboration into the boot camp. Seven novice anaesthesiology trainees and 3 anaesthetic nurses attended 3 4-h boot camp sessions. The boot camp consisted of the following: (1) interactive didactic lectures; (2) task-trainer technical skills teaching; and, (3) high-fidelity simulations. Pre- and post-course evaluation forms including a multiple-choice-questions (MCQ) assessing knowledge were completed. Nine participants fully completed the boot camp. There was a significant increase in post-MCQ score (p = 0.001). Feedback from participants included “well organised”, “helpful” and “structured approach” with all participants agreeing or strongly agreeing that it was relevant training for their practice. We have created the first Irish anaesthesiology boot camp, demonstrating the important role that simulation has in enhancing medical education. Our results showed both knowledge attainment and participant satisfaction in this method of learning. Anaesthesiology boot camps are the ideal method to provide novice trainees with a framework for their initial introduction into anaesthesia.

In this paper we analyze the effects of using nonlinear least squares for parameter identification of symbolic regression models and integrate it as local search mechanism in tree-based genetic programming. We employ the Levenberg–Marquardt algorithm for parameter optimization and calculate gradients via automatic differentiation. We provide examples where the parameter identification succeeds and fails and highlight its computational overhead. Using an extensive suite of symbolic regression benchmark problems we demonstrate the increased performance when incorporating nonlinear least squares within genetic programming. Our results are compared with recently published results obtained by several genetic programming variants and state of the art machine learning algorithms. Genetic programming with nonlinear least squares performs among the best on the defined benchmark suite and the local search can be easily integrated in different genetic programming algorithms as long as only differentiable functions are used within the models.

The present research aims to establish the impact that the current crisis situation the planet is facing, namely the COVID-19 pandemic, has had so far on the Romanian labor force market. In this context, given the lack of information and information regarding this pandemic and its effects, the administration of a questionnaire among the population was considered to identify the research results. The method of semantic differential and the method of ordering the ranks were used for the interpretation of the results. With the help of this questionnaire, it will be possible to answer the question of the research in this study: What are the main effects of the COVID-19 pandemic on the Romanian labor market? The main results showed that the COVID-19 pandemic affected the Romanian workforce, the respondents of the applied questionnaire claimed that they obtained better results and maintained a similar income, but the health crisis also influenced the mentality of employees, with respondents stating that in the event of changing jobs, they would consider it very important for the new employer to ensure the conditions for preventing and combating COVID-19, as well as complex health insurance. However, analyzing at the macroeconomic level, it was found that the COVID-19 pandemic induced an increase in the number of unemployed people in the Romanian labor market.

Sudden cardiac death (SCD) represents a major cause of death in end-stage kidney disease (ESKD). The precise estimate of its incidence is difficult to establish because studies on the incidence of SCD in ESKD are often combined with those related to sudden cardiac arrest (SCA) occurring during a haemodialysis (HD) session. The aim of the European Dialysis Working Group of ERA-EDTA was to critically review the current literature examining the causes of extradialysis SCD and intradialysis SCA in ESKD patients and potential management strategies to reduce the incidence of such events. Extradialysis SCD and intradialysis SCA represent different clinical situations and should be kept distinct. Regarding the problem, numerically less relevant, of patients affected by intradialysis SCA, some modifiable risk factors have been identified, such as a low concentration of potassium and calcium in the dialysate, and some advantages linked to the presence of automated external defibrillators in dialysis units have been documented. The problem of extra-dialysis SCD is more complex. A reduced left ventricular ejection fraction associated with SCD is present only in a minority of cases occurring in HD patients. This is the proof that SCD occurring in ESKD has different characteristics compared with SCD occurring in patients with ischaemic heart disease and/or heart failure and not affected by ESKD. Recent evidence suggests that the fatal arrhythmia in this population may be due more frequently to bradyarrhythmias than to tachyarrhythmias. This fact may partly explain why several studies could not demonstrate an advantage of implantable cardioverter defibrillators in preventing SCD in ESKD patients. Electrolyte imbalances, frequently present in HD patients, could explain part of the arrhythmic phenomena, as suggested by the relationship between SCD and timing of the HD session. However, the high incidence of SCD in patients on peritoneal dialysis suggests that other risk factors due to cardiac comorbidities and uraemia per se may contribute to sudden mortality in ESKD patients.

Assistive devices developed for visually impaired users help them understand the environment so they can navigate with minimum additional help. Such devices greatly rely on image processing techniques to distinguish essential features from the input images. The ground surface represents one key element that needs to be detected. The user can move freely on the ground surface but also obstacles are usually located on this surface. As assistive devices need to provide information in real time, any designed algorithm must achieve real time results. In this paper, we present a novel algorithm to detect the ground plane in video sequences. The sequences are acquired by a stereo camera worn by a visually impaired user. Our algorithm uses a V-disparity map approach and it is tailored for the challenges that arise from the fact that the stereo camera has six degrees-of-freedom. We evaluate the accuracy of our algorithm using multiple real life scenarios. An evaluation of the performances of the algorithm was also performed to prove its accuracy and speed. We also discuss a possible speed up of the proposed algorithm but at a minor cost of accuracy.

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality among patients with end-stage renal disease (ESRD). Clustering of traditional atherosclerotic and non-traditional risk factors drive the excess rates of coronary and non-coronary CVD in this population. The incidence, severity and mortality of coronary artery disease (CAD) as well as the number of complications of its therapy is higher in dialysis patients than in non-chronic kidney disease patients. Given the lack of randomized clinical trial evidence in this population, current practice is informed by observational data with a significant potential for bias. Furthermore, guidelines lack any recommendation for these patients or extrapolate them from trials performed in non-dialysis patients. Patients with ESRD are more likely to be asymptomatic, posing a challenge to the correct identification of CAD, which is essential for appropriate risk stratification and management. This may lead to “therapeutic nihilism”, which has been associated with worse outcomes. Here, the ERA-EDTA EUDIAL Working Group reviews the diagnostic work-up and therapy of chronic coronary syndromes, unstable angina/non-ST elevation and ST-elevation myocardial infarction in dialysis patients, outlining unclear issues and controversies, discussing recent evidence, and proposing management strategies. Indications of antiplatelet and anticoagulant therapies, percutaneous coronary intervention and coronary artery bypass grafting are discussed. The issue of the interaction between dialysis session and myocardial damage is also addressed.

(1) Background: Data suggest that patients with coronary chronic total occlusion (CTO) managed with percutaneous coronary intervention (PCI) could have better outcomes than those treated with optimal medical therapy alone. We aimed to systematically review dedicated scoring systems used to predict successful PCI in patients with CTO. (2) Methods: Electronic databases of MEDLINE (PubMed), Embase, and Cochrane were searched. (3) Results: 32 studies were included. We provided insights into all available predictive models of PCI success in CTO including predictive performance, validations, and comparisons between different scores and models’ limitations. Considering the differences in the population included, coronary lesions, and techniques applied across clinical studies, the most used scores displayed a modest to good predictive value, as follows: J-CTO (AUC, 0.55–0.868), PROGRESS-CTO (AUC, 0.557–0.788), CL (AUC, 0.624–0.800), CASTLE (AUC, 0.633–0.68), and KCCT (AUC, 0.703–0.776). As PCI for CTO is one of the most complex interventions, using dedicated scoring systems could ensure an adequate case selection as well as preparation for an appropriate recanalization technique in order to increase chances of successful procedure. (4) Conclusion: Clinical models appear to be valuable tools for the prediction of PCI success in CTO patients. Clinicians should be aware of the limitations of each model and should be able to correctly select the most appropriate score according to real-life case particularities such as lesion complexity and operator experience in order to maximize success and achieve the best patients’ outcomes.

During the last decade, a growing prevalence of new psychoactive substances (NPS) has been noticed by the law enforcement agencies. Although NPS have no medical use due to their very high toxicity, they are often sold on the black market. NBOMe defines a group of toxic amphetamines that has as parent compound 25I-NBOMe, a synthetic derivative of 2C-I (2,5-dimethoxy-4-iodophenetylamine). In this paper, we are presenting a series of Artificial Neural Networks (ANNs) designed to identify the NBOMe class membership based on a mixture of topological and 3D-MoRSE descriptors. For this purpose, the molecular structures of 160 compounds representing NBOMe compounds, narcotics, sympathomimetic amines, potent analgesics, as well as their main precursors have been first optimized. Then a molecular database was formed by computing a large number of topological and 3D-MoRSE descriptors that characterize these structures. This database was used as input for building an ANN system designed to recognize NBOMes. The relevance of the input variables on its classification performance has been assessed and new systems have been built by using different combinations of selected topological and 3D-MoRSE descriptors. The best performing system has been found by comparing various classification efficiency criteria.

Background and Objectives: Two-dimensional speckle tracking echocardiography (2D-STE) is viewed as an outstanding technique, competent of uncovering earlier subclinical myocardial anomalies compared to conventional echocardiography. A few endeavors adopted 2D-STE as a tool to estimate right ventricular (RV) function in subjects with end-stage kidney disease (ESKD). There is no published prospective study on an adult ESKD cohort exploring the consequences of commencing elective hemodialysis (HD) on RV behavior. Materials and Methods: We investigated the RV systolic function using traditional (tricuspid annular plane systolic excursion—TAPSE, RV fractional area change—FAC) and 2D-STE (RV free wall longitudinal strain—RVFWLS) parameters following the initiation of HD. We enrolled 79 consecutive patients with ESKD and assessed them in four steps—at baseline, before HD, and at 3, 6, and 12 months. Results: RVFWLS, FAC, and TAPSE values had a significant increase at 3, 6, and 12 months from baseline (p &lt, 0.001) and a significant increase at 6 months from 3 months (p &lt, 0.001). However, differences between 12 months and 6 months were not significant (p &gt, 0.05) according to Dunn–Bonferroni post hoc tests. Seventeen deaths were recorded before the completion of the study. RVFWLS, FAC, and TAPSE values significantly decreased at 3 and 6 months in all 17 deceased patients, in clear opposition with the values survivors had. All the studied parameters had a significant prediction power on mortality (p &lt, 0.001) having an outstanding performance: baseline-RVFWLS (AUC: 1.000 (95% C.I.: 1.000–1.000)), baseline-FAC (AUC: 0.974 (95% C.I.: 0.942–1.000)), and baseline-TAPSE (AUC: 0.962 (95% C.I.: 0.920–1.000). Conclusions: Our study is the first to investigate RV function by 2D-STE and correlate it with traditional methods in patients with ESKD before and after the initiation of HD. RV function was significantly ameliorated at 3, 6, and 12 months compared to the pre-HD values. FAC and RVFWLS gain an outstanding prognostic role on mortality in this population.

This chapter explores public opinion on healthcare from both theoretical and empirical perspectives. It critically reviews the literature surrounding public opinion on healthcare, teasing out the main concepts used—support for public healthcare provision/spending, overall evaluations of the healthcare systems, and the political salience of healthcare—while also discussing implications, gaps, and potential new research avenues. The chapter examines the operationalization of these key measures in large-scale survey items and compares trends in Europe over time. While Europeans mostly agree that it is the government’s responsibility to ensure adequate healthcare, there is much more regional variation when it comes to satisfaction with healthcare systems, and their political salience. The chapter concludes by arguing for the need to further examine the link between these key public opinion measures and their impact on health policy reform.

For most visually impaired people, simple tasks such as understanding the environment or moving safely around it represent huge challenges. The Sound of Vision system was designed as a sensory substitution device, based on computer vision techniques, that encodes any environment in a naturalistic representation through audio and haptic feedback. The present paper presents a study on the usability of this system for visually impaired people in relevant environments. The aim of the study is to assess how well the system is able to help the perception and mobility of the visually impaired participants in real life environments and circumstances. The testing scenarios were devised to allow the assessment of the added value of the Sound of Vision system compared to traditional assistive instruments, such as the white cane. Various data were collected during the tests to allow for a better evaluation of the performance: system configuration, completion times, electro-dermal activity, video footage, user feedback. With minimal training, the system could be successfully used in outdoor environments to perform various perception and mobility tasks. The benefit of the Sound of Vision device compared to the white cane was confirmed by the participants and by the evaluation results to consist in: providing early feedback about static and dynamic objects, providing feedback about elevated objects, walls, negative obstacles (e.g., holes in the ground) and signs.

BackgroundWith the introduction of strict public health measures due to the coronavirus pandemic, we have had to change how we deliver simulation training. In order to reinstate the College of Anaesthesiologists Simulation Training (CAST) programme safely, we have had to make significant logistical changes. We discuss the process of reopening a national simulation anaesthesiology programme during a pandemic.MethodsWe approached how to reinstate the programme with three distinct but intertwined projects, as in the following: (1) a survey of effects of the pandemic on training opportunities for anaesthesiology trainees, (2) proposals for methods of reinstating simulation were developed under the headings avoidance, compromise, accommodation and collaboration. A small online video-assisted simulation pilot was carried out to test the compromise method, (3) having opted for combined accommodation (onsite with smaller participant numbers and safety measures) and collaboration (with other regional centres), a postreinstatement evaluation during a 4-month period was carried out.Results(1) Eighty-five per cent of 64 trainees surveyed felt that they had missed out not only just on simulation-based education (43%) but also on other training opportunities, (2) when five trainees were asked to state on a 1 to 5 Likert scale (strongly disagree, disagree, undecided, agree and strongly agree) whether online video-assisted simulation was similar to face-to-face simulation in four categories (realism, immersion, sense of crisis and stress), only 9 (45%) of the 20 answers agreed they were similar, (3) When onsite simulation was reinstated, the majority of trainees felt that training was similar to prepandemic and were happy to continue with this format.ConclusionIn order to reinstate simulation, we have identified that accommodation and collaboration best suited the CAST while compromise failed to rank high among trainees’ preferences. Onsite courses will continue to be delivered safely while meeting the high standards our trainees have come to expect.

Obesity and type 2 diabetes mellitus have become a significant public health problem in the past decades. Their prevalence is increasing worldwide each year, greatly impacting the economic and personal aspects, mainly because they frequently coexist, where the term “diabesity” may be used. The drug class of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) is one of the most modern therapy options in managing these metabolic disorders. This review focuses on the effects of liraglutide, a long-acting GLP-1 RA, in diabesity and non-diabetic excess weight. This drug class improves glycemic control by enhancing insulin secretion from the beta-pancreatic cells and inhibiting glucagon release. Furthermore, other effects include slowing gastric emptying, increasing postprandial satiety, and reducing the appetite and food consumption by influencing the central nervous system, with weight reduction effects. It also reduces cardiovascular events and has positive effects on blood pressure and lipid profile. A lower-dose liraglutide (1.2 or 1.8 mg/day) is used in patients with diabetes, while the higher dose (3.0 mg/day) is approved as an anti-obesity drug. In this review, we have summarized the role of liraglutide in clinical practice, highlighting its safety and efficacy as a glucose-lowering agent and a weight-reduction drug in patients with and without diabetes.

Objectives. We aimed to analyse data from our high-volume interventional centre (>1000 primary percutaneous coronary interventions (PCI) per year) searching for predictors of in-hospital mortality in acute myocardial infarction (MI) patients. Moreover, we looked for realistic strategies and interventions for lowering in-hospital mortality under the “5 percent threshold.” Background. Although interventional and medical treatment options are constantly expanding, recent studies reported a residual in-hospital mortality ranging between 5 and 10 percent after primary PCI. Current data sustain that mortality after ST-elevation MI will soon reach a point when cannot be reduced any further. Methods. In this retrospective observational single-centre cohort study, we investigated two-year data from a primary PCI registry including 2035 consecutive patients. Uni- and multivariate analysis were performed to identify independent predictors for in-hospital mortality. Results. All variables correlated with mortality in univariate analysis were introduced in a stepwise multivariate linear regression model. Female gender, hypertension, depressed left ventricular ejection fraction, history of MI, multivessel disease, culprit left main stenosis, and cardiogenic shock proved to be independent predictors of in-hospital mortality. The model was validated for sensitivity and specificity using receiver operating characteristic curve. For our model, variables can predict in-hospital mortality with a specificity of 96.60% and a sensitivity of 84.68% (p<0.0001, AUC = 0.93, 95% CI 0.922–0.944). Conclusions. Our analysis identified a predictive model for in-hospital mortality. The majority of deaths were due to cardiogenic shock. We suggested that in order to lower mortality under 5 percent, focus should be on creating a cardiogenic shock system based on the US experience. A shock hub-centre, together with specific transfer algorithms, mobile interventional teams, ventricular assist devices, and surgical hybrid procedures seem to be the next step toward a better management of ST-elevation MI patients and subsequently lower death rates.

We show that ML–Mc is a viable and regionally portable depth discriminant, and therefore may contribute to nuclear test ban treaty verification. A recent study found that the difference between local magnitude (ML) and coda duration magnitude (Mc) discriminates shallow seismic events (mining blasts, mining‐induced earthquakes, and shallow tectonic earthquakes) from deeper tectonic earthquakes in the Utah region. The shallow seismic events had anomalously high Mc values, with increasingly negative ML–Mc values as depth decreased. Here, we evaluate the performance of ML–Mc as a depth discriminant in three new regions and find that ML–Mc increases between 0 and 9 km depth in all cases. Initially, we investigated ML–Mc as a function of depth for naturally occurring earthquakes in the region around Yellowstone National Park, as recorded by the University of Utah Seismograph Stations. For 3358 Yellowstone earthquakes with well‐constrained depths, we found ML–Mc increased 0.030±0.007 magnitude units (m.u.) for each 1 km increase in depth up to 10 km depth. Next, we examined ML–Mc values for anthropogenic seismicity in northern Oklahoma and southern Kansas, as recorded by the National Earthquake Information Center. For 1628 events with well‐constrained depths, we computed a slope for ML–Mc of 0.022±0.010 m.u./km. Finally, we analyzed ML–Mc for 28,722 well‐located earthquakes in Italy, as recorded by the National Institute of Geophysics and Volcanology, and found an ML–Mc slope of 0.018±0.001 m.u./km. In each case, the quoted error bounds represent 95% confidence regions that exclude zero, implying that the depth dependence of ML–Mc is statistically significant. We performed several robustness tests in which we varied the criterion used to define a well‐constrained depth and the depth range used in the linear fit. In nearly all cases, we found a positive slope for ML–Mc versus depth at a confidence level above 95%.

HIV-associated neurocognitive disorder (HAND) is characterized by chronic immune activation. We aimed to identify biomarkers associated with HAND and to investigate their association with cognitive function and sex, in a homogenous cohort of HIV-infected (HIV+) young adults, parenterally infected during early childhood. One hundred forty-four HIV+ Romanian participants (51% women) without major confounders underwent standardized neurocognitive and medical evaluation in a cross-sectional study. IFN-γ, IL-1β, IL-6, CCL2, CXCL8, CXCL10, and TNF-α were measured in plasma in all participants and in cerebrospinal fluid (CSF) in a subgroup of 56 study participants. Biomarkers were compared with neurocognitive outcomes, and the influence of sex and HIV disease biomarkers was assessed. In this cohort of young adults (median age of 24years), the rate of neurocognitive impairment (NCI) was 36.1%. Median current CD4+ count was 479cells/mm3 and 36.8% had detectable plasma viral load. Women had better HIV-associated overall status. In plasma, controlling for sex, higher levels of IL-6 and TNF-α were associated with NCI (p

Moisture-sensitive or collapsible soils are materials with high porosity that under the loads transmitted by the superstructure or even under its own weight present additional settlements once the soil is saturated. This category includes loess deposits and other high silt content soils with uneven porosity. A method often used for foundation on these soils is the realization of local loessoid material compacted columns. This paper presents, on one hand, the experimental laboratory programs aiming to achieve some optimal mixtures of local material (loess) and different other materials (sand, bentonite, cement) in order to improve the values of the mechanical parameters of the soil and so, to limit the settlements. On the other hand, it presents a lot of settlement calculations for different case scenarios.

Low-density lipoprotein cholesterol (LDL-C) levels almost constantly increased in patients with nephrotic syndrome (NS). Protein convertase subtilisin/kexin type 9 (PCSK9) [accelerates LDL-receptor (LDL-R) degradation] is overexpressed by liver cells in NS. Their levels, correlated inversely to LDL-R expression and directly to LDL-C, seem to play a central role in hypercholesterolaemia in NS. Hypersynthesis resulting from sterol regulatory element-binding protein dysfunction, hyperactivity induced by c-inhibitor of apoptosis protein expressed in response to stimulation by tumour necrosis factor-α produced by damaged podocytes and hypo-clearance are the main possible mechanisms. Increased LDL-C may damage all kidney cell populations (podocytes, mesangial and tubular cells) in a similar manner. Intracellular cholesterol accumulation produces oxidative stress, foam cell formation and apoptosis, all favoured by local inflammation. The cumulative effect of cellular lesions is worsened proteinuria and kidney function loss. Accordingly, NS patients should be considered high risk and treated by lowering LDL-C. However, there is still not enough evidence determining whether lipid-lowering agents are helpful in managing dyslipidaemia in NS. Based on good efficacy and safety proved in the general population, therapeutic modulation of PCSK9 via antibody therapy might be a reasonable solution. This article explores the established and forthcoming evidence implicating PCSK9 in LDL-C dysregulation in NS.

Nontraditional cardiovascular risk factors such as lipoprotein(a) (Lp(a)), the genetic polymorphisms of apolipoprotein(a), apolipoprotein E (ApoE), and apolipoprotein B (ApoB) increase the prevalence of atherosclerosis in end-stage renal disease (ESRD) through quantitative and qualitative alterations. Given the high burden of cardiovascular fatal events in ESRD, this review aims to gather studies depicting apolipoproteins’ changes in ESRD, to describe current evidence and to explore potential lipid-lowering therapies. We searched the electronic database of PubMed, SCOPUS, EBSCO, and Cochrane CENTRAL for studies evaluating apolipoproteins in ESRD. Randomized controlled trials, observational studies (including case–control, prospective, or retrospective cohort), and reviews/meta-analysis were included if reference was made to apolipoproteins and cardiovascular consequences in ESRD. 21 studies met the inclusion criteria. We found a significant correlation between Lp(a) plasma concentrations and atherosclerosis. Lp(a) levels were independent risk factors for atherothrombosis and cardiovascular mortality. LMW apo(a) phenotype proved to be the best predictor for coronary events in ESRD. Single nucleotide polymorphisms in ApoE gene affected the expression and function of the protein, increasing the risk of cardiovascular events. ApoB had a significant correlation with the value of carotid intima–media thickness and vascular stiffness. The picture of “lipid milieu” in ESRD has not been clearly described. Novel studies show that specific apolipoproteins suffer modifications in uremic patients, being correlated with cardiovascular events. Probably in the next years, the treatment of dyslipidemia in ESRD will not merely target LDL or total cholesterol, but specific isoforms of apolipoproteins which seem to become the central part of the problem.

Heart failure with preserved ejection fraction (HFpEF) is a common disorder generating high mortality and important morbidity prevalence, with a very limited medical treatment available. Studies have shown that the pathophysiological hallmark of this condition is an elevated left intra-atrial pressure (LAP), exertional dyspnea being its clinical manifestation. The increasing pressure from LA is not based on volume overload (such as in heart failure with reduced ejection fraction) but on a diastolic left ventricular (LV) dysfunction combined with an inter-atrial dyssynchrony mimicking a pseudo-pacemaker syndrome. In this review, we aimed to summarize current knowledge and discuss future directions of the newest interventional percutaneous therapies of HFpEF. Novel interventional approaches developed to counter these mechanisms are as follows: LA decompression (inter-atrial shunt devices), enhancement of LV compliance (LV expanders), and inter-atrial resynchronization therapy (LA permanent pacing). To date, inter-atrial shunt devices (IASD) are the most studied, being the only devices currently tested in a phase 3 trial. Recent data showed that IASD are feasible, safe, and have a short-term clinical benefit in HFpEF patients. LV expanders and LA pacing therapy present with a smaller clinical benefit compared with IASD, but they are safe, without any major adverse outcomes currently noted. With further development and improvement of these mechanism-specific devices, it will be interesting to determine in the future whether a complex intervention of multiple HFpEF device implantation will be safe and have further benefits in HFpEF patients.