Self-organized stable pacemakers near the onset of birhythmicity

General amplitude equations for reaction-diffusion systems near to the soft onset of birhythmicity described by a supercritical pitchfork-Hopf bifurcation are derived. Using these equations and applying singular perturbation theory, we show that stable autonomous pacemakers represent a generic kind of spatiotemporal patterns in such systems. This is verified by numerical simulations, which also show the existence of breathing and swinging pacemaker solutions. The drift of self-organized pacemakers in media with spatial parameter gradients is analytically and numerically investigated.Comment: 4 pages, 4 figure

Clinical and electrophysiological predictors of device-detected new-onset atrial fibrillation during 3 years after cardiac surgery

Postoperative atrial fibrillation (POAF) after cardiac surgery is an independent predictor of stroke and mortality late after discharge. We aimed to determine the burden and predictors of early (up to 5th postoperative day) and late (after 5th postoperative day) new-onset atrial fibrillation (AF) using implantable loop recorders (ILRs) in patients undergoing open chest cardiac surgery Seventy-nine patients without a history of AF undergoing cardiac surgery underwent peri-operative high-resolution mapping of electrically induced AF and were followed 36 months after surgery using an ILR (Reveal XTTM). Clinical and electrophysiological predictors of late POAF were assessed. POAF occurred in 46 patients (58%), with early POAF detected in 27 (34%) and late POAF in 37 patients (47%). Late POAF episodes were short-lasting (mostly between 2 min and 6 h) and showed a circadian rhythm pattern with a peak of episode initiation during daytime. In POAF patients, electrically induced AF showed more complex propagation patterns than in patients without POAF. Early POAF, right atrial (RA) volume, prolonged PR time, and advanced age were independent predictors of late POAF

Evaluation of Combined Artificial Intelligence and Radiologist Assessment to Interpret Screening Mammograms

Importance: Mammography screening currently relies on subjective human interpretation. Artificial intelligence (AI) advances could be used to increase mammography screening accuracy by reducing missed cancers and false positives. Objective: To evaluate whether AI can overcome human mammography interpretation limitations with a rigorous, unbiased evaluation of machine learning algorithms. Design, Setting, and Participants: In this diagnostic accuracy study conducted between September 2016 and November 2017, an international, crowdsourced challenge was hosted to foster AI algorithm development focused on interpreting screening mammography. More than 1100 participants comprising 126 teams from 44 countries participated. Analysis began November 18, 2016. Main Outcomes and Measurements: Algorithms used images alone (challenge 1) or combined images, previous examinations (if available), and clinical and demographic risk factor data (challenge 2) and output a score that translated to cancer yes/no within 12 months. Algorithm accuracy for breast cancer detection was evaluated using area under the curve and algorithm specificity compared with radiologists' specificity with radiologists' sensitivity set at 85.9% (United States) and 83.9% (Sweden). An ensemble method aggregating top-performing AI algorithms and radiologists' recall assessment was developed and evaluated. Results: Overall, 144 231 screening mammograms from 85 580 US women (952 cancer positive ≤12 months from screening) were used for algorithm training and validation. A second independent validation cohort included 166 578 examinations from 68 008 Swedish women (780 cancer positive). The top-performing algorithm achieved an area under the curve of 0.858 (United States) and 0.903 (Sweden) and 66.2% (United States) and 81.2% (Sweden) specificity at the radiologists' sensitivity, lower than community-practice radiologists' specificity of 90.5% (United States) and 98.5% (Sweden). Combining top-performing algorithms and US radiologist assessments resulted in a higher area under the curve of 0.942 and achieved a significantly improved specificity (92.0%) at the same sensitivity. Conclusions and Relevance: While no single AI algorithm outperformed radiologists, an ensemble of AI algorithms combined with radiologist assessment in a single-reader screening environment improved overall accuracy. This study underscores the potential of using machine learning methods for enhancing mammography screening interpretation

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Life-threatening infections in children in Europe (the EUCLIDS Project): a prospective cohort study

Background: Sepsis and severe focal infections represent a substantial disease burden in children admitted to hospital. We aimed to understand the burden of disease and outcomes in children with life-threatening bacterial infections in Europe. Methods: The European Union Childhood Life-threatening Infectious Disease Study (EUCLIDS) was a prospective, multicentre, cohort study done in six countries in Europe. Patients aged 1 month to 18 years with sepsis (or suspected sepsis) or severe focal infections, admitted to 98 participating hospitals in the UK, Austria, Germany, Lithuania, Spain, and the Netherlands were prospectively recruited between July 1, 2012, and Dec 31, 2015. To assess disease burden and outcomes, we collected demographic and clinical data using a secured web-based platform and obtained microbiological data using locally available clinical diagnostic procedures. Findings: 2844 patients were recruited and included in the analysis. 1512 (53·2%) of 2841 patients were male and median age was 39·1 months (IQR 12·4–93·9). 1229 (43·2%) patients had sepsis and 1615 (56·8%) had severe focal infections. Patients diagnosed with sepsis had a median age of 27·6 months (IQR 9·0–80·2), whereas those diagnosed with severe focal infections had a median age of 46·5 months (15·8–100·4; p<0·0001). Of 2844 patients in the entire cohort, the main clinical syndromes were pneumonia (511 [18·0%] patients), CNS infection (469 [16·5%]), and skin and soft tissue infection (247 [8·7%]). The causal microorganism was identified in 1359 (47·8%) children, with the most prevalent ones being Neisseria meningitidis (in 259 [9·1%] patients), followed by Staphylococcus aureus (in 222 [7·8%]), Streptococcus pneumoniae (in 219 [7·7%]), and group A streptococcus (in 162 [5·7%]). 1070 (37·6%) patients required admission to a paediatric intensive care unit. Of 2469 patients with outcome data, 57 (2·2%) deaths occurred: seven were in patients with severe focal infections and 50 in those with sepsis. Interpretation: Mortality in children admitted to hospital for sepsis or severe focal infections is low in Europe. The disease burden is mainly in children younger than 5 years and is largely due to vaccine-preventable meningococcal and pneumococcal infections. Despite the availability and application of clinical procedures for microbiological diagnosis, the causative organism remained unidentified in approximately 50% of patients

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection ar

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. The 'omics' approaches to identifying biomarkers from the host-response to bacterial infection are promising. In this study, lipidomic analysis was carried out with plasma samples obtained from febrile children with confirmed bacterial infection (n = 20) and confirmed viral infection (n = 20). We show for the first time that bacterial and viral infection produces distinct profile in the host lipidome. Some species of glycerophosphoinositol, sphingomyelin, lysophosphatidylcholine and cholesterol sulfate were higher in the confirmed virus infected group, while some species of fatty acids, glycerophosphocholine, glycerophosphoserine, lactosylceramide and bilirubin were lower in the confirmed virus infected group when compared with confirmed bacterial infected group. A combination of three lipids achieved an area under the receiver operating characteristic (ROC) curve of 0.911 (95% CI 0.81 to 0.98). This pilot study demonstrates the potential of metabolic biomarkers to assist clinicians in distinguishing bacterial from viral infection in febrile children, to facilitate effective clinical management and to the limit inappropriate use of antibiotics

Health Care Provider Value Chain

International audienceIn every society there is a need for an efficient health care system. This paper aims to propose a value definition and a value chain model within the health care. In order to define value patients and experts were surveyed. The proposed definition offers a complex way of looking at the value within the health care sector. The proposal of the value chain model is anticipated with a value stream mapping activities and experts interviews. Proposed model offers consistent way of looking at the value chain from health care provider perspective

Fatigue-Induced Scapular Dyskinesis in Healthy Overhead Athletes

Alterations of scapular kinematics affect the whole kinematic chain, potentially leading to the impingement syndrome. This is crucial in overhead sports, where athletes perform frequent and quick upper limb actions. In this manuscript, we aimed to assess the extent to which fatigue alters scapulo-thoracic and scapulo-humeral ranges of motion (RoM), as well as scapulo-humeral movement onset during different upper limb actions. Twenty-four young healthy males aged 22 ± 2 years (height: 1.82 ± 0.06 m, body mass: 78.0 ± 7.8 kg) performed three movements (upper limb elevation, scapular-plane abduction, and intra-extra rotation) before and after an isokinetic fatigue protocol (upper limb intra/extra rotation, 32 repetitions at 120 degrees/s). Pre vs. post fatigue RoM of humeral elevation and rotation, scapular retraction/protraction, and rotation and tilt were computed. Humerus-scapula movement delay was also determined. Humerus elevation range reduced during intra/extra humerus rotation in fatigued conditions (p = 0.006). Scapular tilt RoM increased after the fatigue protocol (p = 0.063, large effect). Humerus-scapular movement onset delay reduced in fatigued conditions of about 80 ms (p &lt; 0.001, large effect). In sum, fatigued intra/extra upper limb rotators altered the scapulohumeral rhythm, and joints RoM in movements outside the scapular plane. Rather, movements close to the scapular plane were less prone to fatigue-induced alterations

Body size and shape characteristics for Cooper's 12 minutes run test in 11-13 years old Caucasian children: An allometric approach

This is an accepted manuscript of an article published by Edizioni Minerva Medica in Journal of Sports Medicine and Physical Fitness on 20/03/2020, available online: https://www.minervamedica.it/en/journals/sports-med-physical-fitness/article.php?cod=R40Y2020N03A0417 The accepted version of the publication may differ from the final published version.�� 2019 EDIZIONI MINERVA MEDICA. BACKGROUND: The Cooper Test, is a field test, simple and useful in the school context. The aim of this research was the definition of the trend in Cooper endurance test along with the growth. In particular, through the scaling method (allometric). METHODS: Atotal of 556 of European sedentary children aged 11-13 years (282 boys; 274 girls) were involved. All subjects were evaluated through the Endurance Cooper test (12 min run test). To identify the most appropriate body size and shape characteristics as well as any categorical differences (sex, age) associated with the measure of the Cooper test, a multiplicative model with allometric body-size components was applied. RESULTS: The multiplicative model relating to the Cooper test and the body-size components was: Cooper test = a mass-0.325 �� height0.878 with the mass and height exponents being k1=-0.325 (SEE=0.40) and k2= 0.878 (SEE=0.141), respectively. The adjusted coefficient of determination (adj R2) was 32.3%, with a log-transformed error ratio of 0.136 or 14.5% having taken antilogs. Significant differences in the constant 'a' parameter were identified by sex (P<0.001) and age (P<0.001) while the interaction of sex per age was not significant (P=0.761). CONCLUSIONS: The results suggested that the scaling method identified the optimal height-to-body mass ratios associated with Cooper endurance test corresponding to ectomorph body shape. Furthermore, growth fluctuations become important to avoid alarming judgment in case children will be poorly evaluated.Published versio