Objective-Brain-computer interface (BCI) technology can provide severely disabled people with non-muscular communication. For those most severely disabled, limitations in eye mobility or visual acuity may necessitate auditory BCI systems. The present study investigates the efficacy of the use of six environmental sounds to operate a 6×6 P300 Speller.Methods-A two-group design was used to ascertain whether participants benefited from visual cues early in training. Group A (N=5) received only auditory stimuli during all 11 sessions, whereas Group AV (N=5) received simultaneous auditory and visual stimuli in initial sessions after which the visual stimuli were systematically removed. Stepwise linear discriminant analysis determined the matrix item that elicited the largest P300 response and thereby identified the desired choice.Results-Online results and offline analyses showed that the two groups achieved equivalent accuracy. In the last session, eight of ten participants achieved 50% or more, and four of these achieved 75% or more, online accuracy (2.8% accuracy expected by chance). Mean bit rates averaged about 2 bits/min, and maximum bit rates reached 5.6 bits/min.Conclusions-This study indicates that an auditory P300 BCI is feasible, that reasonable classification accuracy and rate of communication are achievable, and that the paradigm should be further evaluated with a group of severely disabled participants who have limited visual mobility.Significance-With further development, this auditory P300 BCI could be of substantial value to severely disabled people who cannot use a visual BCI.
Exfoliation syndrome (XFS) is the commonest known risk factor for secondary glaucoma and a significant cause of blindness worldwide. Variants in two genes, LOXL1 and CACNA1A have been previously associated with XFS. To further elucidate the genetic basis of XFS, we collected a global sample of XFS cases to refine the association at LOXL1, which previously showed inconsistent results between populations, and to identify new variants associated with XFS. We identified a rare, protective allele at LOXL1 (p.407Phe, OR = 25, P =2.9 × 10−14) through deep resequencing of XFS cases and controls from 9 countries. This variant results in increased cellular adhesion strength compared to the wild-type (p.407Tyr) allele. A genome-wide association study (GWAS) of XFS cases and controls from 24 countries followed by replication in 18 countries identified seven genome-wide significant loci (P < 5 × 10−8). Index variants at the new loci map to chromosomes 13q12 (POMP), 11q23.3 (TMEM136), 6p21 (AGPAT1), 3p24 (RBMS3) and 5q23 (near SEMA6A). These findings provide biological insights into the pathology of XFS, and highlight a potential role for naturally occurring rare LOXL1 variants in disease biology.
BackgroundSepsis 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.MethodsData 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 death. Secondary outcome measures were PICU-free days censured at day 28, hospital length of stay, and disability. Independent predictors were identified by multivariate regression analysis.ResultsPatients most commonly presented clinically with sepsis without a source (n = 278, 35%), meningitis/encephalitis (n = 182, 23%), or pneumonia (n = 149, 19%). Of 428 (54%) patients with confirmed bacterial infection, Neisseria meningitidis (n = 131, 31%) and Streptococcus pneumoniae (n = 78, 18%) were the main pathogens. Mortality was 6% (51/795), increasing to 10% in the presence of septic shock (45/466). Of the survivors, 31% were discharged with disability, including 24% of previously healthy children who survived with disability. Mortality and disability were independently associated with S. pneumoniae infections (mortality OR 4.1, 95% CI 1.1–16.0, P = 0.04; disability OR 5.4, 95% CI 1.8–15.8, P < 0.01) and illness severity as measured by Pediatric Index of Mortality (PIM2) score (mortality OR 2.8, 95% CI 1.3–6.1, P < 0.01; disability OR 3.4, 95% CI 1.8–6.4, P < 0.001).ConclusionsDespite widespread immunization campaigns, invasive bacterial disease remains responsible for substantial morbidity and mortality in critically ill children in high-income countries. Almost one third of sepsis survivors admitted to the PICU were discharged with some disability. More research is required to delineate the long-term outcome of pediatric sepsis and to identify interventional targets. Our findings emphasize the importance of improved early sepsis-recognition programs to address the high burden of disease.Electronic supplementary materialThe online version of this article (10.1186/s13054-018-2052-7) contains supplementary material, which is available to authorized users.
Only 4 out of the 36 evaluated formulas gave mean differences between measured and calculated osmolality of less than 1 mosmol/kg H(2)O. Zander's novel formula showed excellent concordance with measured osmolality and facilitates a more precise diagnosis based on blood gas analysers. The new equation has the potential to replace separate measurements of osmolality in many cases.
Objective: Within this work an auditory P300 brain-computer interface (BCI) based on tone stream segregation, which allows for binary decisions, was developed and evaluated. Materials and methods: Two tone streams consisting of short beep tones with infrequently appearing deviant tones at random positions were used as stimuli. This paradigm was evaluated in 10 healthy subjects and applied to 12 patients in a minimally conscious state (MCS) at clinics in Graz, Würzburg, Rome, and Liège. A stepwise linear discriminant analysis (SWLDA) classifier with 10 × 10 cross-validation was used to 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 than random. However, for MCS patients only a small number of classification results were above chance level and none of the results were sufficient for communication purposes. Nevertheless, signs of consciousness were detected in most patients, not on a single-trial basis, but after averaging of corresponding data segments and computing significant differences. These significant results, however, strongly varied across sessions and conditions. Conclusion: This work shows the transition of a paradigm from healthy subjects to MCS patients. Promising results with healthy subjects are, however, no guarantee of good results with patients. Therefore, more investigations are required before any definite conclusions about the usability of this paradigm for MCS patients can be drawn. Nevertheless, this paradigm might offer an opportunity to support bedside clinical assessment of MCS patients and eventually, to provide them with a means of communication.
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