Feasibility, efficacy, and functional relevance of automated auditory closed-loop suppression of slow-wave sleep in humans.

Slow-wave sleep (SWS) is a fundamental physiological process, and its modulation is of interest for basic science and clinical applications. However, automatised protocols for the suppression of SWS are lacking. We describe the development of a novel protocol for the automated detection (based on the whole head topography of frontal slow waves) and suppression of SWS (through closed-loop modulated randomised pulsed noise), and assessed the feasibility, efficacy and functional relevance compared to sham stimulation in 15 healthy young adults in a repeated-measure sleep laboratory study. Auditory compared to sham stimulation resulted in a highly significant reduction of SWS by 30% without affecting total sleep time. The reduction of SWS was associated with an increase in lighter non-rapid eye movement sleep and a shift of slow-wave activity towards the end of the night, indicative of a homeostatic response and functional relevance. Still, cumulative slow-wave activity across the night was significantly reduced by 23%. Undisturbed sleep led to an evening to morning reduction of wake electroencephalographic theta activity, thought to reflect synaptic downscaling during SWS, while suppression of SWS inhibited this dissipation. We provide evidence for the feasibility, efficacy, and functional relevance of a novel fully automated protocol for SWS suppression based on auditory closed-loop stimulation. Future work is needed to further test for functional relevance and potential clinical applications.

Extending outbreak investigation with machine learning and graph theory: Benefits of new tools with application to a nosocomial outbreak of a multidrug-resistant organism.

OBJECTIVE: From January 1, 2018, until July 31, 2020, our hospital network experienced an outbreak of vancomycin-resistant enterococci (VRE). The goal of our study was to improve existing processes by applying machine-learning and graph-theoretical methods to a nosocomial outbreak investigation. METHODS: We assembled medical records generated during the first 2 years of the outbreak period (January 2018 through December 2019). We identified risk factors for VRE colonization using standard statistical methods, and we extended these with a decision-tree machine-learning approach. We then elicited possible transmission pathways by detecting commonalities between VRE cases using a graph theoretical network analysis approach. RESULTS: We compared 560 VRE patients to 86,684 controls. Logistic models revealed predictors of VRE colonization as age (aOR, 1.4 (per 10 years), with 95% confidence interval [CI], 1.3-1.5; P < .001), ICU admission during stay (aOR, 1.5; 95% CI, 1.2-1.9; P < .001), Charlson comorbidity score (aOR, 1.1; 95% CI, 1.1-1.2; P < .001), the number of different prescribed antibiotics (aOR, 1.6; 95% CI, 1.5-1.7; P < .001), and the number of rooms the patient stayed in during their hospitalization(s) (aOR, 1.1; 95% CI, 1.1-1.2; P < .001). The decision-tree machine-learning method confirmed these findings. Graph network analysis established 3 main pathways by which the VRE cases were connected: healthcare personnel, medical devices, and patient rooms. CONCLUSIONS: We identified risk factors for being a VRE carrier, along with 3 important links with VRE (healthcare personnel, medical devices, patient rooms). Data science is likely to provide a better understanding of outbreaks, but interpretations require data maturity, and potential confounding factors must be considered.

Computational Evidence for Laboratory Diagnostic Pathways: Extracting Predictive Analytes for Myocardial Ischemia from Routine Hospital Data.

Background: Laboratory parameters are critical parts of many diagnostic pathways, mortality scores, patient follow-ups, and overall patient care, and should therefore have underlying standardized, evidence-based recommendations. Currently, laboratory parameters and their significance are treated differently depending on expert opinions, clinical environment, and varying hospital guidelines. In our study, we aimed to demonstrate the capability of a set of algorithms to identify predictive analytes for a specific diagnosis. As an illustration of our proposed methodology, we examined the analytes associated with myocardial ischemia; it was a well-researched diagnosis and provides a substrate for comparison. We intend to present a toolset that will boost the evolution of evidence-based laboratory diagnostics and, therefore, improve patient care. Methods: The data we used consisted of preexisting, anonymized recordings from the emergency ward involving all patient cases with a measured value for troponin T. We used multiple imputation technique, orthogonal data augmentation, and Bayesian Model Averaging to create predictive models for myocardial ischemia. Each model incorporated different analytes as cofactors. In examining these models further, we could then conclude the predictive importance of each analyte in question. Results: The used algorithms extracted troponin T as a highly predictive analyte for myocardial ischemia. As this is a known relationship, we saw the predictive importance of troponin T as a proof of concept, suggesting a functioning method. Additionally, we could demonstrate the algorithm's capabilities to extract known risk factors of myocardial ischemia from the data. Conclusion: In this pilot study, we chose an assembly of algorithms to analyze the value of analytes in predicting myocardial ischemia. By providing reliable correlations between the analytes and the diagnosis of myocardial ischemia, we demonstrated the possibilities to create unbiased computational-based guidelines for laboratory diagnostics by using computational power in today's era of digitalization.

Data-driven reduction of dendritic morphologies with preserved dendro-somatic responses.

Dendrites shape information flow in neurons. Yet, there is little consensus on the level of spatial complexity at which they operate. Through carefully chosen parameter fits, solvable in the least-squares sense, we obtain accurate reduced compartmental models at any level of complexity. We show that (back-propagating) action potentials, Ca2+ spikes, and N-methyl-D-aspartate spikes can all be reproduced with few compartments. We also investigate whether afferent spatial connectivity motifs admit simplification by ablating targeted branches and grouping affected synapses onto the next proximal dendrite. We find that voltage in the remaining branches is reproduced if temporal conductance fluctuations stay below a limit that depends on the average difference in input resistance between the ablated branches and the next proximal dendrite. Furthermore, our methodology fits reduced models directly from experimental data, without requiring morphological reconstructions. We provide software that automatizes the simplification, eliminating a common hurdle toward including dendritic computations in network models.