Drops on Polymer Brushes: Advances in Thin-Film Modeling of Adaptive Substrates.

We briefly review recent advances in the hydrodynamic modeling of the dynamics of droplets on adaptive substrates, in particular, solids that are covered by polymer brushes. Thereby, the focus is on long-wave and full-curvature variants of mesoscopic hydrodynamic models in gradient dynamics form. After introducing the approach for films/drops of nonvolatile simple liquids on a rigid smooth solid substrate, it is first expanded to an arbitrary number of coupled degrees of freedom before considering the specific case of drops of volatile liquids on brush-covered solids. After presenting the model, its usage is illustrated by briefly considering the natural and forced spreading of drops of nonvolatile liquids on a horizontal brush-covered substrate, stick-slip motion of advancing contact lines as well as drops sliding down a brush-covered incline. Finally, volatile liquids are also considered.

Preliminary evidence of transcutaneous vagus nerve stimulation effects on sleep in veterans with post-traumatic stress disorder.

Sleep problems are common among veterans with post-traumatic stress disorder and closely associated with hyperarousal symptoms. Transcutaneous vagus nerve stimulation (tVNS) may have potential to improve sleep quality in veterans with PTSD through effects on brain systems relevant to hyperarousal and sleep-wake regulation. The current pilot study examines the effect of 1 h of tVNS administered at "lights out" on sleep architecture, microstructure, and autonomic activity. Thirteen veterans with PTSD completed two nights of laboratory-based polysomnography during which they received 1 h of either active tVNS (tragus) or sham stimulation (earlobe) at "lights out" with randomised order. Sleep staging and stability metrics were derived from polysomnography data. Autonomic activity during sleep was assessed using the Porges-Bohrer method for calculating respiratory sinus arrhythmia (RSAP-B ). Paired t-tests revealed a small decrease in the total sleep time (d = -0.31), increase in N3 sleep (d = 0.23), and a small-to-moderate decrease in REM sleep (d = -0.48) on nights of active tVNS relative to sham stimulation. tVNS was also associated with a moderate reduction in cyclic alternating pattern (CAP) rate (d = -0.65) and small-to-moderate increase in RSAP-B during NREM sleep. Greater NREM RSAP-B was associated with a reduced CAP rate and NREM alpha power. This pilot study provides preliminary evidence that tVNS may improve sleep depth and stability in veterans with PTSD, as well as increase parasympathetically mediated nocturnal autonomic activity. These results warrant continued investigation into tVNS as a potential tool for treating sleep disturbance in veterans with PTSD.

Transvenous phrenic nerve stimulation for treating central sleep apnea may regulate sleep microstructure.

STUDY OBJECTIVES: To assess the impact of transvenous phrenic nerve stimulation (TPNS) on non-rapid eye movement sleep microstructure quantified by cyclic alternating pattern (CAP) in individuals with central sleep apnea (CSA). METHODS: We analyzed baseline and 6-month follow-up overnight polysomnograms (PSG) in 134 CSA patients enrolled in the remede System Pivotal Trial implanted with TPNS randomized (1:1) to neurostimulation (treatment group) or no stimulation (control group). Differences in CAP rate, A1 index, and A2+A3 index between study arms at follow-up were assessed using Analysis of Covariance adjusted for baseline values. RESULTS: On follow-up PSG, the treatment group showed a decrease in the frequency of A2+A3 phases compared to controls (-5.86 ± 11.82 vs. 0.67 ± 15.25, p = 0.006), while the frequency of A1 phases increased more in the treatment group (2.57 ± 11.67 vs. -2.47 ± 10.60, p = 0.011). The change in CAP rate at follow-up was comparable between study arms. CONCLUSIONS: TPNS treatment for central sleep apnea may affect sleep microstructure. Brief phases of rapid cortical activity appear to be replaced by short phases of slower cortical activity, which may promote sleep continuity. Further investigations are warranted to elucidate the mechanisms underlying the effect of TPNS on CAP.

Combining Clinical With Cognitive or Magnetic Resonance Imaging Data for Predicting Transition to Psychosis in Ultra High-Risk Patients: Data From the PACE 400 Cohort.

BACKGROUND: Multimodal modeling that combines biological and clinical data shows promise in predicting transition to psychosis in individuals who are at ultra-high risk. Individuals who transition to psychosis are known to have deficits at baseline in cognitive function and reductions in gray matter volume in multiple brain regions identified by magnetic resonance imaging. METHODS: In this study, we used Cox proportional hazards regression models to assess the additive predictive value of each modality-cognition, cortical structure information, and the neuroanatomical measure of brain age gap-to a previously developed clinical model using functioning and duration of symptoms prior to service entry as predictors in the Personal Assessment and Crisis Evaluation (PACE) 400 cohort. The PACE 400 study is a well-characterized cohort of Australian youths who were identified as ultra-high risk of transitioning to psychosis using the Comprehensive Assessment of At Risk Mental States (CAARMS) and followed for up to 18 years; it contains clinical data (from N = 416 participants), cognitive data (n = 213), and magnetic resonance imaging cortical parameters extracted using FreeSurfer (n = 231). RESULTS: The results showed that neuroimaging, brain age gap, and cognition added marginal predictive information to the previously developed clinical model (fraction of new information: neuroimaging 0%-12%, brain age gap 7%, cognition 0%-16%). CONCLUSIONS: In summary, adding a second modality to a clinical risk model predicting the onset of a psychotic disorder in the PACE 400 cohort showed little improvement in the fit of the model for long-term prediction of transition to psychosis.

Subject-level Normalization to Improve A-phase Detection of Cyclic Alternating Pattern in Sleep EEG.

Automatic detection systems for activation phases (A-phase) of the cyclic alternating pattern (CAP) in electroencephalograms (EEG) are designed to automatically score A-phases in any individual but typically fail to factor in EEG signal variations between individuals, e.g. due to sleep disorders, recording site differences or equipment differences. Here, we investigate the effect of subject-level normalization on the performance of an automatic A-phase detection system consisting of a recurrent neural network. We compared the classification performance of various subject-level normalization methods to the standard training set normalization. Systems were trained and tested on subjects with different sleep disorders using the publicly available CAP Sleep Database on Physionet. Subject-level normalization using Zscore or median and interquartile range (IQR) increases the F1-score for A1-phases by +11-22% (Z-Score: +11-20%, Median/IQR: +16-22%), for A2-phases by +2-9% (Z-Score: +59%, Median/IQR: +2-7%), for A3-phases by -1 - +8% (Z-Score: +3-8%, Median/IQR: -1-+5%) as compared to the standard training data normalization when tested across sleep disorders. Our results show that subject-level normalization drastically improves the precision of A-phase detection in case the training population differs from the testing population.Clinical Relevance- Subject-level normalisation improves the automatic CAP scoring system performances for the general population by minimizing the effect of individual EEG differences.

Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder.

Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental health disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N = 2367) and replicated in the combined PsyCourse (N = 89) and BipoLife (N = 102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P < 0.05. Li+PGS was positively associated with lithium treatment response in the ConLi+Gen cohort, in both the categorical (P = 9.8 × 10-12, R2 = 1.9%) and continuous (P = 6.4 × 10-9, R2 = 2.6%) outcomes. Compared to bipolar patients in the 1st decile of the risk distribution, individuals in the 10th decile had 3.47-fold (95%CI: 2.22-5.47) higher odds of responding favorably to lithium. The results were replicated in the independent cohorts for the categorical treatment outcome (P = 3.9 × 10-4, R2 = 0.9%), but not for the continuous outcome (P = 0.13). Gene-based analyses revealed 36 candidate genes that are enriched in biological pathways controlled by glutamate and acetylcholine. Li+PGS may be useful in the development of pharmacogenomic testing strategies by enabling a classification of bipolar patients according to their response to treatment.

Nonequilibrium configurations of swelling polymer brush layers induced by spreading drops of weakly volatile oil.

Polymer brush layers are responsive materials that swell in contact with good solvents and their vapors. We deposit drops of an almost completely wetting volatile oil onto an oleophilic polymer brush layer and follow the response of the system upon simultaneous exposure to both liquid and vapor. Interferometric imaging shows that a halo of partly swollen polymer brush layer forms ahead of the moving contact line. The swelling dynamics of this halo is controlled by a subtle balance of direct imbibition from the drop into the brush layer and vapor phase transport and can lead to very long-lived transient swelling profiles as well as nonequilibrium configurations involving thickness gradients in a stationary state. A gradient dynamics model based on a free energy functional with three coupled fields is developed and numerically solved. It describes experimental observations and reveals how local evaporation and condensation conspire to stabilize the inhomogeneous nonequilibrium stationary swelling profiles. A quantitative comparison of experiments and calculations provides access to the solvent diffusion coefficient within the brush layer. Overall, the results highlight the-presumably generally applicable-crucial role of vapor phase transport in dynamic wetting phenomena involving volatile liquids on swelling functional surfaces.

Stick-slip dynamics in the forced wetting of polymer brushes.

We study the static and dynamic wetting of adaptive substrates using a mesoscopic hydrodynamic model for a liquid droplet on a solid substrate covered by a polymer brush. First, we show that on the macroscale Young's law still holds for the equilibrium contact angle and that on the mesoscale a Neumann-type law governs the shape of the wetting ridge. Following an analytic and numeric assessment of the static profiles of droplet and wetting ridge, we examine the dynamics of the wetting ridge for a liquid meniscus that is advanced at constant mean speed. In other words, we consider an inverse Landau-Levich case where a brush-covered plate is introduced into (and not drawn from) a liquid bath. We find a characteristic stick-slip motion that emerges when the dynamic contact angle of the stationary moving meniscus decreases with increasing velocity, and relate the onset of slip to Gibbs' inequality and to a cross-over in relevant time scales.

Automatic sleep staging for the young and the old - Evaluating age bias in deep learning.

BACKGROUND: Various deep-learning systems have been proposed for automated sleep staging. Still, the significance of age-specific underrepresentation in training data and the resulting errors in clinically used sleep metrics are unknown. METHODS: We adopted XSleepNet2, a deep neural network for automated sleep staging, to train and test models using polysomnograms of 1232 children (7.0 ± 1.4 years) and 3757 adults (56.9 ± 19.4 years) and 2788 older adults (mean 80.7 ± 4.2 years). We developed four separate sleep stage classifiers using exclusively pediatric (P), adult (A), older adults (O) as well as PSG from mixed cohorts: pediatric, adult, and older adult (PAO). Results were compared against an alternative sleep stager (DeepSleepNet) for validation purposes. RESULTS: When pediatric PSG was classified by XSleepNet2 exclusively trained on pediatric PSG, the overall accuracy was 88.9%, dropping to 78.9% when subjected to a system trained exclusively on adult PSG. Errors performed by the system staging PSG of older people were comparably lower. However, all systems produced significant errors in clinical markers when considering individual PSG. Results obtained with DeepSleepNet showed similar patterns. CONCLUSION: Underrepresentation of age groups, in particular children, can significantly lower the performance of automatic deep-learning sleep stagers. In general, automated sleep stagers may behave unexpectedly, limiting clinical use. Future evaluation of automated systems must pay attention to PSG-level performance and overall accuracy.

Association of Polygenic Score and the involvement of Cholinergic and Glutamatergic Pathways with Lithium Treatment Response in Patients with Bipolar Disorder.

Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N=2,367) and replicated in the combined PsyCourse (N=89) and BipoLife (N=102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P<����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������.

Association between psychotropic medication and sleep microstructure: evidence from large population studies.

STUDY OBJECTIVES: To assess the association between psychotropic medications and sleep microstructure in large community-based cohorts of older people. METHODS: We analyzed overnight polysomnograms of 381 women from the Study of Osteoporotic Fractures (SOF) and 2,657 men from the Osteoporotic Fractures in Men Sleep Study (MrOS), who either used no psychotropic medication (n = 2,819), only benzodiazepines (n = 112), or only selective serotonin reuptake inhibitors (SSRI) (n = 107). Sleep microstructure (cyclic alternating pattern, CAP) was compared between the no medication group and psychotropic medication groups using the Mann-Whitney U test. Significant differences were investigated using multivariable linear regression adjusted for confounders. RESULTS: CAP rate, arousal index, apnea-hypopnea index, and the frequency of slow, low-amplitude electroencephalography activation phases were significantly lower in MrOS participants using benzodiazepines than participants not taking psychotropic medication. SSRI users in MrOS experienced no altered sleep microstructure compared to those with no psychotropic use. SOF participants using benzodiazepines did not show similar associations with sleep microstructure. However, SSRI users from SOF had a significantly higher frequency of rapid, high-amplitude electroencephalography activation phases (A2 + 3) and periodic limb-movement index than participants not taking psychotropic medication. Multivariable linear regression adjusted for demographic, lifestyle, mood disorders, and health variables indicated additional significant associations between benzodiazepine usage and CAP rate and A2 + 3 index, respectively, in older men, and between CAP rate and SSRI usage in older women. CONCLUSIONS: We identified significant associations between sleep microstructure and psychotropic drugs in MrOS and SOF, highlighting the importance of comprehensive sleep analysis, including CAP. Our results may improve understanding of the differences in sleep-wake mechanisms based on psychotropic usage. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Title: Outcomes of Sleep Disorders in Older Men; Identifier: NCT00070681; URL: https://clinicaltrials.gov/ct2/show/record/NCT00070681. CITATION: Hartmann S, Parrino L, Ensrud K, et al. Association between psychotropic medication and sleep microstructure: evidence from large population studies. J Clin Sleep Med. 2023;19(3):581-589.

Beyond the nation-state: Anchoring supranational institutions in international business research.

In this paper, we broaden the conceptualization of institutions beyond the nation-state and develop the concept of an institutional triality that represents two national institutional environments and the supranational level. While much of international business (IB) research has focused on national institutions and the differences between them, little attention and theorizing has been dedicated to the supranational institutions that form an integral part of the global institutional ecosystem. First, we conduct an interdisciplinary bibliometric survey on supranational institutions and a qualitative review of the central publications. Second, we initiate theory building and conceptualize supranational institutions from an IB point of view, distinguish them from related IB concepts, and discuss the conceptual properties of supranational institutions that are most relevant for MNCs. Building on these distinctions and properties, we provide a conceptual framework for understanding supranational institutions in the institutional triality. Third, we provide avenues for IB research building on the delineations, the conceptual properties, and the conceptual framework. Supplementary Information: The online version contains supplementary material available at 10.1057/s41267-022-00537-3.

Dans cet article, nous élargissons la conceptualisation des institutions au-delà de l'État-nation et développons le concept de trialité institutionnelle qui représente deux environnements institutionnels nationaux et le niveau supranational. Alors qu'une grande partie de la recherche en affaires internationales (International Business - IB) s'est focalisée sur les institutions nationales et les différences entre elles, peu d'attention et d'effort de théorisation sont consacrés aux institutions supranationales qui font partie intégrante de l'écosystème institutionnel global. Dans un premier temps, nous réalisons une enquête bibliométrique interdisciplinaire sur les institutions supranationales et une revue qualitative des principales publications. Ensuite, nous commençons la construction théorique et conceptualisons les institutions supranationales dans une perspective de l'IB. Nous les distinguons des concepts connexes de l'IB et discutons des propriétés conceptuelles des institutions supranationales qui sont les plus pertinentes pour les entreprises multinationales. Nous appuyant sur ces distinctions et ces propriétés, nous apportons un cadre conceptuel permettant de comprendre les institutions supranationales dans la trialité institutionnelle. Enfin, nous proposons des pistes de recherche en IB en partant sur les délimitations, les propriétés conceptuelles et le cadre conceptuel.

En este trabajo ampliamos la conceptualización de las instituciones más allá del estado nación y desarrollamos el concepto de trialidad institucional que representa dos entornos institucionales nacionales y el nivel supranacional. Mientras que mucha de la investigación en negocios internacionales se ha enfocado en las instituciones nacionales y las diferencias entre ellas, poca atención y teorización se ha dedicado a las instituciones supranacionales que forman parte integral del ecosistema institucional global. Primero, llevamos a cabo un sondeo bibliométrico interdisciplinario sobre las instituciones supranacionales y una revisión cualitativa de las publicaciones centrales. Segundo, iniciamos una construcción teórica y a conceptualizar las instituciones supranacionales desde el punto de vista de negocios internacionales, diferenciándolas de otros conceptos relacionados en negocios internacionales, y discutimos las propiedades conceptuales de las instituciones supranacionales que son más relevantes para las empresas multinacionales. En base en estas diferencias y propiedades, proporcionamos un marco conceptual para entender las instituciones supranacionales en la trialidad instituciona. Tercero, proporcionamos posibilidades para la investigación en negocios internacionales sobre las delimitaciones, las propiedades conceptuales, y el marco conceptual.

Neste artigo, ampliamos a conceituação de instituições para além do estado-nação e desenvolvemos o conceito de uma trialidade institucional que representa dois ambientes institucionais nacionais e o nível supranacional. Embora grande parte da pesquisa em negócios internacionais (IB) tenha se concentrado em instituições nacionais e nas diferenças entre elas, pouca atenção e teorização são dedicadas às instituições supranacionais que formam uma parte intrínseca do ecossistema institucional global. Primeiramente, realizamos um levantamento bibliométrico interdisciplinar em instituições supranacionais e uma revisão qualitativa das publicações centrais. Em segundo lugar, iniciamos a construção de teoria e conceituamos instituições supranacionais sob o ponto de vista de IB, distinguimo-las de conceitos relacionados a IB e discutimos as propriedades conceituais de instituições supranacionais que são mais relevantes para MNCs. Com base nessas diferenças e propriedades, fornecemos um modelo conceitual para entender as instituições supranacionais na trialidade institucional. Terceiro, fornecemos caminhos para construção de pesquisa em IB sobre delineações, propriedades conceituais e modelo conceitual.

Causality of cortical and cardiovascular activity during cyclic alternating pattern in non-rapid eye movement sleep.

The dynamic interplay between central and autonomic nervous system activities plays a pivotal role in orchestrating sleep. Macrostructural changes such as sleep-stage transitions or phasic, brief cortical events elicit fluctuations in neural outflow to the cardiovascular system, but the causal relationships between cortical and cardiovascular activities underpinning the microstructure of sleep are largely unknown. Here, we investigate cortical-cardiovascular interactions during the cyclic alternating pattern (CAP) of non-rapid eye movement sleep in a diverse set of overnight polysomnograms. We determine the Granger causality in both 507 CAP and 507 matched non-CAP sequences to assess the causal relationships between electroencephalography (EEG) frequency bands and respiratory and cardiovascular variables (heart period, respiratory period, pulse arrival time and pulse wave amplitude) during CAP. We observe a significantly stronger influence of delta activity on vascular variables during CAP sequences where slow, low-amplitude EEG activation phases (A1) dominate than during non-CAP sequences. We also show that rapid, high-amplitude EEG activation phases (A3) provoke a more pronounced change in autonomic activity than A1 and A2 phases. Our analysis provides the first evidence on the causal interplay between cortical and cardiovascular activities during CAP. Granger causality analysis may also be useful for probing the level of decoupling in sleep disorders. This article is part of the theme issue 'Advanced computation in cardiovascular physiology: new challenges and opportunities'.

Sleep arousal burden is associated with long-term all-cause and cardiovascular mortality in 8001 community-dwelling older men and women.

AIMS: To quantify the arousal burden (AB) across large cohort studies and determine its association with long-term cardiovascular (CV) and overall mortality in men and women. METHODS AND RESULTS: We measured the AB on overnight polysomnograms of 2782 men in the Osteoporotic Fractures in Men Study (MrOS) Sleep study, 424 women in the Study of Osteoporotic Fractures (SOF) and 2221 men and 2574 women in the Sleep Heart Health Study (SHHS). During 11.2 ± 2.1 years of follow-up in MrOS, 665 men died, including 236 CV deaths. During 6.4 ± 1.6 years of follow-up in SOF, 105 women died, including 47 CV deaths. During 10.7 ± 3.1 years of follow-up in SHHS, 987 participants died, including 344 CV deaths. In women, multivariable Cox proportional hazard analysis adjusted for common confounders demonstrated that AB is associated with all-cause mortality [SOF: hazard ratio (HR) 1.58 (1.01-2.42), P = 0.038; SHHS-women: HR 1.21 (1.06-1.42), P = 0.012] and CV mortality [SOF: HR 2.17 (1.04-4.50), P = 0.037; SHHS-women: HR 1.60 (1.12-2.28), P = 0.009]. In men, the association between AB and all-cause mortality [MrOS: HR 1.11 (0.94-1.32), P = 0.261; SHHS-men: HR 1.31 (1.06-1.62), P = 0.011] and CV mortality [MrOS: HR 1.35 (1.02-1.79), P = 0.034; SHHS-men: HR 1.24 (0.86-1.79), P = 0.271] was less clear. CONCLUSIONS: Nocturnal AB is associated with long-term CV and all-cause mortality in women and to a lesser extent in men.

Cyclic alternating pattern in children with obstructive sleep apnea and its relationship with adenotonsillectomy, behavior, cognition, and quality of life.

STUDY OBJECTIVES: To determine in children with obstructive sleep apnea (OSA) the effect of adenotonsillectomy (AT) on the cyclic alternating pattern (CAP) and the relationship between CAP and behavioral, cognitive, and quality-of-life measures. METHODS: CAP parameters were analyzed in 365 overnight polysomnographic recordings of children with mild-to-moderate OSA enrolled in the Childhood Adenotonsillectomy Trial (CHAT), randomized to either early AT (eAT) or watchful waiting with supportive care (WWSC). We also analyzed CAP in a subgroup of 72 children with moderate OSA (apnea-hypopnea index > 10) that were part of the CHAT sample. Causal mediation analysis was performed to determine the independent effect of changes in CAP on selected outcome measures. RESULTS: At baseline, a higher number of A1 phases per hour of sleep was significantly associated with worse behavioral functioning (caregiver Behavior Rating Inventory of Executive Function (BRIEF) Global Executive Composite (GEC): ρ = 0.24, p = 0.042; caregiver Conners' Rating Scale Global Index: ρ = 0.25, p = 0.036) and lower quality of life (OSA-18: ρ = 0.27, p = 0.022; PedsQL: ρ = -0.29, p = 0.015) in the subgroup of children with moderate OSA, but not across the entire sample. At 7-months follow-up, changes in CAP parameters were comparable between the eAT and WWSC arms. CAP changes did not account for significant proportions of variations in behavioral, cognitive, and quality-of-life performance measures at follow-up. CONCLUSIONS: We show a significant association between the frequency of slow, high-amplitude waves with behavioral functioning, as well as the quality of life in children with moderate OSA. Early AT in children with mild-to-moderate OSA does not alter the microstructure of nonrapid eye movement sleep compared with watchful waiting after an approximately 7-month period of follow-up. CLINICAL TRIAL: The study "A Randomized Controlled Study of Adenotonsillectomy for Children With Obstructive Sleep Apnea Syndrome" was registered at Clinicaltrials.gov (#NCT00560859).

Non-REM sleep instability in children with restless sleep disorder.

STUDY OBJECTIVES: Restless sleep disorder (RSD) is a newly recognized condition characterized by motor movements involving large muscle groups with frequent repositioning or bed sheets disruption. We analyzed cyclic alternating pattern (CAP) in these children, a marker of sleep instability that might be associated with the motor episodes of RSD and may play a role in their daytime symptoms. METHODS: Polysomnographic recordings from thirty-eight children who fulfilled RSD diagnostic criteria (23 boys and 15 girls), 23 children with restless legs syndrome (RLS, 18 boys and 5 girls) and 19 controls (10 boys and 9 girls) were included. For CAP analysis, a previously developed, highly precise automated system, based on a deep learning recurrent neural network, was used. RESULTS: Age and gender were not statistically different between groups. RSD patients showed a lower percentage of A3 CAP subtypes than controls (median 9.8 vs. 18.2, p = 0.0089), accompanied by shorter duration of the B phase of the CAP cycle (median 28.2 vs. 29.8 in controls, 30.2 in RLS, p = 0.005) and shorter CAP cycle duration than both controls and RLS subjects (median 33.8 vs. 35.0 in controls, 35.8 in RLS, p = 0.002). Finally, RSD children also showed a longer duration of CAP cycle sequences, when compared to controls (median 172.7 vs. 141.9, p = 0.0063). CONCLUSIONS: In conclusion, our study indicates that NREM sleep EEG shows an increased instability in RSD; these findings add to the current knowledge on the mechanisms of this newly recognized sleep disorder and suggest that sleep instability might be a favoring mechanism for the emergence of the motor episodes characterizing RSD.

Sources and sinks of chloromethane in a salt marsh ecosystem: constraints from concentration and stable isotope measurements of laboratory incubation experiments.

Chloromethane (CH3Cl) is the most abundant long-lived chlorinated organic compound in the atmosphere and contributes significantly to natural stratospheric ozone depletion. Salt marsh ecosystems including halophyte plants are a known source of atmospheric CH3Cl but estimates of their total global source strength are highly uncertain and knowledge of the major production and consumption processes in the atmosphere-halophyte-soil system is yet incomplete. In this study we investigated the halophyte plant, Salicornia europaea, and soil samples from a coastal salt marsh site in Sardinia/Italy for their potential to emit and consume CH3Cl and using flux measurements, stable isotope techniques and Arrhenius plots differentiated between biotic and abiotic processes. Our laboratory approach clearly shows that at least 6 different production and consumption processes are active in controlling atmospheric CH3Cl fluxes of a salt marsh ecosystem. CH3Cl release by dried plant and soil material was substantially higher than that from the fresh material at temperatures ranging from 20 to 70 °C. Results of Arrhenius plots helped to distinguish between biotic and abiotic formation processes in plants and soils. Biotic CH3Cl consumption rates were highest at 30 °C for plants and 50 °C for soils, and microbial uptake was higher in soils with higher organic matter content. Stable isotope techniques helped to distinguish between formation and degradation processes and also provided a deeper insight into potential methyl moiety donor compounds, such as S-adenosyl-l-methionine, S-methylmethionine and pectin, that might be involved in the abiotic and biotic CH3Cl production processes. Our results clearly indicate that cycling of CH3Cl in salt marsh ecosystems is a result of several biotic and abiotic processes occurring simultaneously in the atmosphere-plant-soil system. Important precursor compounds for biotic and abiotic CH3Cl formation might be methionine derivatives and pectin. All formation and degradation processes are temperature dependent and thus environmental changes might affect the strength of each source and sink within salt marsh ecosystems and thus considerably alter total fluxes of CH3Cl from salt marsh ecosystems to the atmosphere.

Characterization of cyclic alternating pattern during sleep in older men and women using large population studies.

STUDY OBJECTIVES: To assess the microstructural architecture of non-rapid eye movement (NREM) sleep known as cyclic alternating pattern (CAP) in relation to the age, gender, self-reported sleep quality, and the degree of sleep disruption in large community-based cohort studies of older people. METHODS: We applied a high-performance automated CAP detection system to characterize CAP in 2,811 men from the Osteoporotic Fractures in Men Sleep Study (MrOS) and 426 women from the Study of Osteoporotic Fractures (SOF). CAP was assessed with respect to age and gender and correlated to obstructive apnea-hypopnea index, arousal index (AI-NREM), and periodic limb movements in sleep index. Further, we evaluated CAP across levels of self-reported sleep quality measures using analysis of covariance. RESULTS: Age was significantly associated with the number of CAP sequences during NREM sleep (MrOS: p = 0.013, SOF = 0.051). CAP correlated significantly with AI-NREM (MrOS: ρ = 0.30, SOF: ρ = 0.29). CAP rate, especially the A2+A3 index, was inversely related to self-reported quality of sleep, independent of age and sleep disturbance measures. Women experienced significantly fewer A1-phases compared to men, in particular, in slow-wave sleep (N3). CONCLUSIONS: We demonstrate that automated CAP analysis of large-scale databases can lead to new findings on CAP and its subcomponents. We show that sleep disturbance indices are associated with the CAP rate. Further, the CAP rate is significantly linked to subjectively reported sleep quality, independent from traditionally scored markers of sleep fragmentation. Finally, men and women show differences in the microarchitecture of sleep as identified by CAP, despite similar macro-architecture.

Automatic A-Phase Detection of Cyclic Alternating Patterns in Sleep Using Dynamic Temporal Information.

The identification of recurrent, transient perturbations in brain activity during sleep, so called cyclic alternating patterns (CAP), is of significant interest as they have been linked to neurological pathologies. CAP sequences comprise multiple, consecutive cycles of phasic activation (A-phases). Here, we propose a novel, automated system exploiting the dynamical, temporal information in electroencephalography (EEG) recordings for the classification of A-phases and their subtypes. Using recurrent neural networks (RNN), crucial information in the temporal behavior of the EEG is extracted. The automatic classification system is equipped to deal with the biasing issue of imbalanced data sets and uses state-of-the-art signal processing methods to reduce inter-subject variation. To evaluate our system, we applied recordings from the publicly available CAP Sleep Database on Physionet. Our results show that the RNN improved the detection accuracy by 3-5% and the F1-score by approximately 7% on two data sets compared to a normal feed-forward neural network. Our system achieves a sensitivity of approximately 76-78% and F1-score between 63-68%, significantly outperforming existing technologies. Moreover, its sensitivity for subtype classification of 60-63% (A1), 42-45% (A2), and 71-74% (A3) indicates superior multi-class classification performance for CAP detection. In conclusion, we have developed a fully automated high performance CAP scoring system that includes A-phase subtype classification. RNN classifiers yield a significant improvement in accuracy and sensitivity compared to previously proposed systems.

Improved A-phase Detection of Cyclic Alternating Pattern Using Deep Learning.

In recent years, machine learning algorithms have become increasingly popular for analyzing biomedical signals. This includes the detection of cyclic alternating pattern (CAP) in electroencephalography recordings. Here, we investigate the performance gain of a recurrent neural network (RNN) for CAP scoring in comparison to standard classification methods. We analyzed 15 recordings (n1-n15) from the publicly available CAP Sleep Database on Physionet to evaluate each machine learning method. A long short-term memory (LSTM) network increases the accuracy and F1-score by 0.5-3.5% and 3.5-8%, respectively, compared to commonly used classification algorithms such as linear discriminant analysis, k-nearest neighbour or feed-forward neural network. Our results show that by using a LSTM classifier the quantity of correctly detected CAP events can be increased and the number of wrongly classified periods reduced. RNNs significantly improve the precision in CAP scoring by taking advantage of available information from the past for deciding current classification.