Brisk heart rate and EEG changes during execution and withholding of cue-paced foot motor imagery

Cue-paced motor imagery (MI) is a frequently used mental strategy to realize a Brain-Computer Interface (BCI). Recently it has been reported that two MI tasks can be separated with a high accuracy within the first second after cue presentation onset. To investigate this phenomenon in detail we studied the dynamics of motor cortex beta oscillations in EEG and the changes in heart rate (HR) during visual cue-paced foot MI using a go (execution of imagery) vs. nogo (withholding of imagery) paradigm in 16 healthy subjects. Both execution and withholding of MI resulted in a brisk centrally localized beta event-related desynchronization (ERD) with a maximum at ~400 ms and a concomitant HR deceleration. We found that response patterns within the first second after stimulation differed between conditions. The ERD was significantly larger in go as compared to nogo. In contrast the HR deceleration was somewhat smaller and followed by an acceleration in go as compared to nogo. These findings suggest that the early beta ERD reflects visually induced preparatory activity in motor cortex networks. Both the early beta ERD and the HR deceleration are the result of automatic operating processes that are likely part of the orienting reflex (OR). Of interest, however, is that the preparatory cortical activity is strengthened and the HR modulated already within the first second after stimulation during the execution of MI. The subtraction of the HR time course of the nogo from the go condition revealed a slight HR acceleration in the first seconds most likely due to the increased mental effort associated with the imagery process

Mortality and morbidity in community-acquired sepsis in European pediatric intensive care units

Background: Sepsis is one of the main reasons for non-elective admission to pediatric intensive care units (PICUs), but little is known about determinants influencing outcome. We characterized children admitted with community-acquired sepsis to European PICUs and studied risk factors for mortality and disability. Methods: Data were collected within the collaborative Seventh Framework Programme (FP7)-funded EUCLIDS study, which is a prospective multicenter cohort study aiming to evaluate genetic determinants of susceptibility and/or severity in sepsis. This report includes 795 children admitted with community-acquired sepsis to 52 PICUs from seven European countries between July 2012 and January 2016. The primary outcome measure was in-hospital de

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

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

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

Detection of mental imagery and attempted movements in patients with disorders of consciousness using EEG

Further development of an EEG based communication device for patients with disorders of consciousness (DoC) could benefit from addressing the following gaps in knowledge – first, an evaluation of different types of motor imagery; second, an evaluation of passive feet movement as a mean of an initial classifier setup; and third, rapid delivery of biased feedback. To that end we investigated whether complex and / or familiar mental imagery, passive, and attempted feet movement can be reliably detected in patients with DoC using EEG recordings, aiming to provide them with a means of communication. Six patients in a minimally conscious state (MCS) took part in this study. The patients were verbally instructed to perform different mental imagery tasks (sport, navigation), as well as attempted feet movements, to induce distinctive event-related (de)synchronization (ERD/S) patterns in the EEG. Offline classification accuracies above chance level were reached in all three tasks (i.e. attempted feet, sport, and navigation), with motor tasks yielding significant (p<0.05) results more often than navigation (sport: 10 out of 18 sessions; attempted feet: 7 out of 14 sessions; navigation: 4 out of 12 sessions). The passive feet movements, evaluated in one patient, yielded mixed results: whereas time-frequency analysis revealed task-related EEG changes over neurophysiological plausible cortical areas, the classification results were not significant enough (p<0.05) to setup an initial classifier for the detection of attempted movements. Concluding, the results presented in this study are consistent with the current state of the art in similar studies, to which we contributed by comparing different types of mental tasks, notably complex motor imagery and attempted feet movements, within patients. Furthermore, we explored new venues, such as an evaluation of passive feet movement as a mean of an initial classifier setup, and rapid delivery of biased feedback

Brisk heart rate and EEG changes during execution and withholding of cue-paced foot motor imagery

Cue-paced motor imagery is a frequently used mental strategy to realize a Brain-Computer Interace (BCI). Recently it has been reported that 2 motor imagery tasks can be separated with a high accuracy within the first second after cue presentation onset. To investigate this phenomenon in detail we studied the dynamics of motor cortex beta oscillations in EEG and the changes in heart rate (HR) during visual cue-paced foot imagery using a go (execution of imagery) versus nogo (withholding of imagery) paradigm in 16 healthy subjects. Both execution and withholding of motor imagery resulted in a brisk centrally localized beta ERD with a maximum at ~ 400 ms and a concomitant HR deceleration. We found that response patterns within the first second after stimulation differed between conditions. The ERD was significantly larger in go as compared to nogo. In contrast the HR deceleration was somewhat smaller and followed by an acceleration in go as compared to nogo. These findings suggest that the early beta ERD reflects visually induced preparatory activity in motor cortex networks. Both the early beta ERD and HR deceleration are the result of automatic operating processes that are likely part of the orienting reflex. Of interest, however, is that the preparatory cortical activity is strengthened and the HR modulated already within the first second after stimulation during the execution of motor imagery. The subtraction of the HR time course of the nogo from the go condition revealed a slight HR acceleration in the first seconds most likely due to the increased mental effort associated with the imagery process

A Rare Mutation in SPLUNC1 Affects Bacterial Adherence and Invasion in Meningococcal Disease

BACKGROUND Neisseria meningitidis (Nm) is a nasopharyngeal commensal carried by healthy individuals. However, invasive infections occurs in a minority of individuals, with devastating consequences. There is evidence that common polymorphisms are associated with invasive meningococcal disease (IMD), but the contributions of rare variants other than those in the complement system have not been determined. METHODS We identified familial cases of IMD in the UK meningococcal disease study and the European Union Life-Threatening Infectious Disease Study. Candidate genetic variants were identified by whole-exome sequencing of 2 patients with familial IMD. Candidate variants were further validated by in vitro assays. RESULTS Exomes of 2 siblings with IMD identified a novel heterozygous missense mutation in BPIFA1/SPLUNC1. Sequencing of 186 other nonfamilial cases identified another unrelated IMD patient with the same mutation. SPLUNC1 is an innate immune defense protein expressed in the nasopharyngeal epithelia; however, its role in invasive infections is unknown. In vitro assays demonstrated that recombinant SPLUNC1 protein inhibits biofilm formation by Nm, and impedes Nm adhesion and invasion of human airway cells. The dominant negative mutant recombinant SPLUNC1 (p.G22E) showed reduced antibiofilm activity, increased meningococcal adhesion, and increased invasion of cells, compared with wild-type SPLUNC1. CONCLUSIONS A mutation in SPLUNC1 affecting mucosal attachment, biofilm formation, and invasion of mucosal epithelial cells is a new genetic cause of meningococcal disease

The auditory P300-based single-switch brain–computer interface:Paradigm transition from healthy subjects to minimally consciouspatients

Objective: Within this work an auditory P300 brain–computer interface based on tone stream segregation,which allows for binary decisions, was developed and evaluated.Methods and materials: Two tone streams consisting of short beep tones with infrequently appearingdeviant tones at random positions were used as stimuli. This paradigm was evaluated in 10 healthysubjects and applied to 12 patients in a minimally conscious state (MCS) at clinics in Graz, Würzburg,Rome, and Liège. A stepwise linear discriminant analysis classifier with 10 × 10 cross-validation was usedto detect the presence of any P300 and to investigate attentional modulation of the P300 amplitude.Results: The results for healthy subjects were promising and most classification results were better thanrandom. In 8 of the 10 subjects, focused attention on at least one of the tone streams could be detectedon a single-trial basis. By averaging 10 data segments, classification accuracies up to 90.6 % could bereached. However, for MCS patients only a small number of classification results were above chance leveland none of the results were sufficient for communication purposes. Nevertheless, signs of consciousnesswere detected in 9 of the 12 patients, not on a single-trial basis, but after averaging of all correspondingdata segments and computing significant differences. These significant results, however, strongly variedacross sessions and conditions.Conclusion: This work shows the transition of a paradigm from healthy subjects to MCS patients. Promisingresults with healthy subjects are, however, no guarantee of good results with patients. Therefore, moreinvestigations are required before any definite conclusions about the usability of this paradigm for MCSpatients can be drawn. Nevertheless, this paradigm might offer an opportunity to support bedside clinicalassessment of MCS patients and eventually, to provide them with a means of communication