Stochastic Modeling of Central Apnea Events in Preterm Infants

A near-ubiquitous pathology in very low birth weight infants is neonatal apnea, breathing pauses with slowing of the heart and falling blood oxygen. Events of substantial duration occasionally occur after an infant is discharged from the neonatal intensive care unit (NICU). It is not known whether apneas result from a predictable process or from a stochastic process, but the observation that they occur in seemingly random clusters justifies the use of stochastic models. We use a hidden-Markov model to analyze the distribution of durations of apneas and the distribution of times between apneas. The model suggests the presence of four breathing states, ranging from very stable (with an average lifetime of 12 h) to very unstable (with an average lifetime of 10 s). Although the states themselves are not visible, the mathematical analysis gives estimates of the transition rates among these states. We have obtained these transition rates, and shown how they change with post-menstrual age; as expected, the residence time in the more stable breathing states increases with age. We also extrapolated the model to predict the frequency of very prolonged apnea during the first year of life. This paradigm-stochastic modeling of cardiorespiratory control in neonatal infants to estimate risk for severe clinical events-may be a first step toward personalized risk assessment for life threatening apnea events after NICU discharge

Signatures of Subacute Potentially Catastrophic Illness in the ICU: Model Development and Validation

Objectives: Patients in ICUs are susceptible to subacute potentially catastrophic illnesses such as respiratory failure, sepsis, and hemorrhage that present as severe derangements of vital signs. More subtle physiologic signatures may be present before clinical deterioration, when treatment might be more effective. We performed multivariate statistical analyses of bedside physiologic monitoring data to identify such early subclinical signatures of incipient life-threatening illness. Design: We report a study of model development and validation of a retrospective observational cohort using resampling (Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis type 1b internal validation) and a study of model validation using separate data (type 2b internal/external validation). Setting: University of Virginia Health System (Charlottesville), a tertiary-care, academic medical center. Patients: Critically ill patients consecutively admitted between January 2009 and June 2015 to either the neonatal, surgical/trauma/burn, or medical ICUs with available physiologic monitoring data. Interventions: None. Measurements and Main Results: We analyzed 146 patient-years of vital sign and electrocardiography waveform time series from the bedside monitors of 9,232 ICU admissions. Calculations from 30-minute windows of the physiologic monitoring data were made every 15 minutes. Clinicians identified 1,206 episodes of respiratory failure leading to urgent unplanned intubation, sepsis, or hemorrhage leading to multi-unit transfusions from systematic individual chart reviews. Multivariate models to predict events up to 24 hours prior had internally validated C-statistics of 0.61-0.88. In adults, physiologic signatures of respiratory failure and hemorrhage were distinct from each other but externally consistent across ICUs. Sepsis, on the other hand, demonstrated less distinct and inconsistent signatures. Physiologic signatures of all neonatal illnesses were similar. Conclusions: Subacute potentially catastrophic illnesses in three diverse ICU populations have physiologic signatures that are detectable in the hours preceding clinical detection and intervention. Detection of such signatures can draw attention to patients at highest risk, potentially enabling earlier intervention and better outcomes

A New Algorithm for Detecting Central Apnea in Neonates

Apnea of prematurity is an important and common clinical problem, and is often the rate-limiting process in NICU discharge. Accurate detection of episodes of clinically important neonatal apnea using existing chest impedance (CI) monitoring is a clinical imperative. The technique relies on changes in impedance as the lungs fill with air, a high impedance substance. A potential confounder, however, is blood coursing through the heart. Thus, the cardiac signal during apnea might be mistaken for breathing. We report here a new filter to remove the cardiac signal from the CI that employs a novel resampling technique optimally suited to remove the heart rate signal, allowing improved apnea detection. We also develop an apnea detection method that employs the CI after cardiac filtering. The method has been applied to a large database of physiological signals, and we prove that, compared to the presently used monitors, the new method gives substantial improvement in apnea detection

Anemia, Apnea of Prematurity, and Blood Transfusions

Objective To compare the frequency and severity of apneic events in very low birth weight (VLBW) infants before and after blood transfusions using continuous electronic waveform analysis. Study design We continuously collected waveform, heart rate, and oxygen saturation data from patients in all 45 neonatal intensive care unit beds at the University of Virginia for 120 weeks. Central apneas were detected using continuous computer processing of chest impedance, electrocardiographic, and oximetry signals. Apnea was defined as respiratory pauses of \u3e 10, \u3e 20, and \u3e 30 seconds when accompanied by bradycardia ( \u3c 100 beats per minute) and hypoxemia ( \u3c 80% oxyhemoglobin saturation as detected by pulse oximetry). Times of packed red blood cell transfusions were determined from bedside charts. Two cohorts were analyzed. In the transfusion cohort, waveforms were analyzed for 3 days before and after the transfusion for all VLBW infants who received a blood transfusion while also breathing spontaneously. Mean apnea rates for the previous 12 hours were quantified and differences for 12 hours before and after transfusion were compared. In the hematocrit cohort, 1453 hematocrit values from all VLBW infants admitted and breathing spontaneously during the time period were retrieved, and the association of hematocrit and apnea in the next 12 hours was tested using logistic regression. Results Sixty-seven infants had 110 blood transfusions during times when complete monitoring data were available. Transfusion was associated with fewer computer-detected apneic events (P \u3c .01). Probability of future apnea occurring within 12 hours increased with decreasing hematocrit values (P \u3c .001). Conclusions Blood transfusions are associated with decreased apnea in VLBW infants, and apneas are less frequent at higher hematocrits. (J Pediatr 2012;161:417-21)

Progress and Challenges in Coupled Hydrodynamic-Ecological Estuarine Modeling

Numerical modeling has emerged over the last several decades as a widely accepted tool for investigations in environmental sciences. In estuarine research, hydrodynamic and ecological models have moved along parallel tracks with regard to complexity, refinement, computational power, and incorporation of uncertainty. Coupled hydrodynamic-ecological models have been used to assess ecosystem processes and interactions, simulate future scenarios, and evaluate remedial actions in response to eutrophication, habitat loss, and freshwater diversion. The need to couple hydrodynamic and ecological models to address research and management questions is clear because dynamic feedbacks between biotic and physical processes are critical interactions within ecosystems. In this review, we present historical and modern perspectives on estuarine hydrodynamic and ecological modeling, consider model limitations, and address aspects of model linkage, skill assessment, and complexity. We discuss the balance between spatial and temporal resolution and present examples using different spatiotemporal scales. Finally, we recommend future lines of inquiry, approaches to balance complexity and uncertainty, and model transparency and utility. It is idealistic to think we can pursue a theory of everything for estuarine models, but recent advances suggest that models for both scientific investigations and management applications will continue to improve in terms of realism, precision, and accuracy

An atlas of healthy and injured cell states and niches in the human kidney

Understanding kidney disease relies on defining the complexity of cell types and states, their associated molecular profiles and interactions within tissue neighbourhood

Theory of NMR as a local probe for the electronic structure in the mixed state of the high-TcT_c cuprates

We argue that nuclear magnetic resonance experiments are a site-sensitive probe for the electronic spectrum in the mixed state of the high-$T_c$ cuprates. Within a spin-fermion model, we show that the Doppler-shifted electronic spectrum arising from the circulating supercurrent changes the low-frequency behavior of the imaginary part of the spin-susceptibility. For a hexagonal vortex lattice, we predict that these changes lead to {\it (a)} a unique dependence of the $^{63}$Cu spin lattice relaxation rate, $1/T_1$, on resonance frequency, and {\it (b)} a temperature dependence of $T_1$ which varies with frequency. We propose a nuclear quadrupole experiment to study the effects of a uniform supercurrent on the electronic structure and predict that $T_1$ varies with the direction of the supercurrent.Comment: RevTex, 5 pages, 3 figures embedded in the tex

Activity-dependent translation dynamically alters the proteome of the perisynaptic astrocyte process

Within eukaryotic cells, translation is regulated independent of transcription, enabling nuanced, localized, and rapid responses to stimuli. Neurons respond transcriptionally and translationally to synaptic activity. Although transcriptional responses are documented in astrocytes, here we test whether astrocytes have programmed translational responses. We show that seizure activity rapidly changes the transcripts on astrocyte ribosomes, some predicted to be downstream of BDNF signaling. In acute slices, we quantify the extent to which cues of neuronal activity activate translation in astrocytes and show that this translational response requires the presence of neurons, indicating that the response is non-cell autonomous. We also show that this induction of new translation extends into the periphery of astrocytes. Finally, synaptic proteomics show that new translation is required for changes that occur in perisynaptic astrocyte protein composition after fear conditioning. Regulation of translation in astrocytes by neuronal activity suggests an additional mechanism by which astrocytes may dynamically modulate nervous system functioning

Tuning a Resonance in the Fock Space: Optimization of Phonon Emission in a Resonant Tunneling Device

Phonon-assisted tunneling in a double barrier resonant tunneling device can be seen as a resonance in the electron-phonon Fock space which is tuned by the applied voltage. We show that the geometrical parameters can induce a symmetry condition in this space that can strongly enhance the emission of longitudinal optical phonons. For devices with thin emitter barriers this is achieved by a wider collector's barrier.Comment: 4 pages, 3 figures. Figure 1 changed, typos correcte

Clusters of alcohol abstainers and drinkers incorporating motives against drinking: a random survey of 18 to 34 year olds in four cities in four different continents

Objective: The aim of this analysis was to identify alcohol consumption clusters for adolescents and early adults according to attitudes to drinking, motivations against drinking and perceptions associated with alcohol. Method: Interviews were undertaken with people aged 18–34 years old living in four cities in different regions of the world. Multistage random sampling was consistent across the four cities (Ilorin (Nigeria), Wuhan (China), Montevideo (Uruguay) and Moscow (Russia)). The questionnaire was forward and back translated into relevant languages and face-to-face interviewing undertaken. The data were weighted to the population of each city. In total 6235 structured interviews were undertaken (1391 in Ilorin, 1600 in Montevideo, 1604 in Moscow and 1640 in Wuhan). Questions regarding motivation against alcohol consumption (14 items), assessing perceptions (3 items) and attitudes to drinking in certain situations (8 items) were asked of all respondents including abstainers. Factor analysis was initially undertaken to identify highly related correlated variables. Results: Cluster analysis provided a variety of clusters (Ilorin (3 clusters), Montevideo (5), Moscow (4) and Wuhan (4)). At least one cluster in each city was dominated by abstainers and another by heavy episodic drinkers. Variations by city and alcohol consumption patterns existed in regards to variables included. Conclusion: This analysis detailed the city specific motivations against drinking alcohol, and the attitudes towards alcohol consumption. Differences highlight the influence of country/city specific culture, customs, laws, societal norms and traditions