Protocol for the Reconstructing Consciousness and Cognition (ReCCognition) Study

Important scientific and clinical questions persist about general anesthesia despite the ubiquitous clinical use of anesthetic drugs in humans since their discovery. For example, it is not known how the brain reconstitutes consciousness and cognition after the profound functional perturbation of the anesthetized state, nor has a specific pattern of functional recovery been characterized. To date, there has been a lack of detailed investigation into rates of recovery and the potential orderly return of attention, sensorimotor function, memory, reasoning and logic, abstract thinking, and processing speed. Moreover, whether such neurobehavioral functions display an invariant sequence of return across individuals is similarly unknown. To address these questions, we designed a study of healthy volunteers undergoing general anesthesia with electroencephalography and serial testing of cognitive functions (NCT01911195). The aims of this study are to characterize the temporal patterns of neurobehavioral recovery over the first several hours following termination of a deep inhaled isoflurane general anesthetic and to identify common patterns of cognitive function recovery. Additionally, we will conduct spectral analysis and reconstruct functional networks from electroencephalographic data to identify any neural correlates (e.g., connectivity patterns, graph-theoretical variables) of cognitive recovery after the perturbation of general anesthesia. To accomplish these objectives, we will enroll a total of 60 consenting adults aged 20–40 across the three participating sites. Half of the study subjects will receive general anesthesia slowly titrated to loss of consciousness (LOC) with an intravenous infusion of propofol and thereafter be maintained for 3 h with 1.3 age adjusted minimum alveolar concentration of isoflurane, while the other half of subjects serves as awake controls to gauge effects of repeated neurobehavioral testing, spontaneous fatigue and endogenous rest-activity patterns

Effects of Acute Exposures to Carbon Dioxide Upon Cognitive Functions

Large quantities of carbon dioxide (CO2) originate from human metabolism and typically, within spacecraft, remain about 10-fold higher in concentration than at the earth's surface. There have been recurring complaints by crew members of episodes of "mental viscosity" adversely affecting their performance, and there is evidence from the International Space Station (ISS) that associates CO2 levels with reports of headaches by crewmembers. Additionally, there is concern that CO2 may contribute to vision impairment and intracranial pressure that has been observed in some crewmembers. Consequently, flight rules have been employed to control the level of CO2 below 4 mm Hg, which is well below the existing Spacecraft Maximum Allowable Concentration (SMAC) of 10 mm Hg for 24-hour exposures, and 5.3 mm Hg for exposures of 7 to 180 days. However, the flight rule imposed limit, which places additional demands upon resources and current technology, still exceeds the lower bound of the threshold range for reportable headaches (2 - 5 mm Hg). Headaches, while sometime debilitating themselves, are also symptoms that can provide evidence that physiological defense mechanisms have been breached. The causes of the headaches may elicit other subtle adverse effects that occur at CO2 levels well below that for headaches. The concern that CO2 may have effects at levels below the threshold for headaches appears to be substantiated in unexpected findings that CO2 at concentrations below 2 mm Hg substantially reduced some cognitive functions that are associated with the ability to make complex decisions in conditions that are characterized by volatility, uncertainty, complexity, ambiguity, and delayed feedback. These are conditions that could be encountered by crews in off-nominal situations or during the first missions beyond low earth orbit. If findings of the earlier study are confirmed in crew-like subjects, our findings would provide additional evidence that CO2 may need to be controlled at levels that are well below current spacecraft limits. Our study will extend the earlier study to determine if crew-like subjects are similarly effected by CO2. In addition to employing the Strategic Management Simulation tool, we will use the Cognition battery of psychometric measures that are being utilized aboard the ISS. It will be important to learn, by using Cognition, if additional cognitive domains are sensitive to concentrations of CO2 at or below limits currently controlled by flight rules. While spaceflight Cognition data will greatly enhance the knowledge base related to inflight behavioral health and performance, some of the measures may be influenced by fatigue (related to sleep deprivation and or workload) and changes in circadian rhythms. Therefore our use of this battery of tests in a well-controlled, ground-based study that is free of these potential confounding influences will establish a baseline terrestrial data set against which Cognition data collected in flight may be assessed. The findings from this study will be useful to the NASA Toxicology Office and the National Research Council Committee on Toxicology, which assists NASA in setting environmental standards, for revision of the SMAC for CO2, and for designing further studies on effects of CO2 upon cognitive functions

Sleep During Pregnancy: The nuMoM2b Pregnancy and Sleep Duration and Continuity Study

Study Objectives: To characterize sleep duration, timing and continuity measures in pregnancy and their association with key demographic variables. Methods: Multisite prospective cohort study. Women enrolled in the nuMoM2b study (nulliparous women with a singleton gestation) were recruited at the second study visit (16-21 weeks of gestation) to participate in the Sleep Duration and Continuity substudy. Women <18 years of age or with pregestational diabetes or chronic hypertension were excluded from participation. Women wore a wrist activity monitor and completed a sleep log for 7 consecutive days. Time in bed, sleep duration, fragmentation index, sleep efficiency, wake after sleep onset, and sleep midpoint were averaged across valid primary sleep periods for each participant. Results: Valid data were available from 782 women with mean age of 27.3 (5.5) years. Median sleep duration was 7.4 hours. Approximately 27.9% of women had a sleep duration of 9 hours. In multivariable models including age, race/ethnicity, body mass index, insurance status, and recent smoking history, sleep duration was significantly associated with race/ethnicity and insurance status, while time in bed was only associated with insurance status. Sleep continuity measures and sleep midpoint were significantly associated with all covariates in the model, with the exception of age for fragmentation index and smoking for wake after sleep onset. Conclusions: Our results demonstrate the relationship between sleep and important demographic characteristics during pregnancy

Experimental and computational characterization of a modified GEC cell for dusty plasma experiments

A self-consistent fluid model developed for simulations of micro- gravity dusty plasma experiments has for the first time been used to model asymmetric dusty plasma experiments in a modified GEC reference cell with gravity. The numerical results are directly compared with experimental data and the experimentally determined dependence of global discharge parameters on the applied driving potential and neutral gas pressure is found to be well matched by the model. The local profiles important for dust particle transport are studied and compared with experimentally determined profiles. The radial forces in the midplane are presented for the different discharge settings. The differences between the results obtained in the modified GEC cell and the results first reported for the original GEC reference cell are pointed out

A cross-sectional exploratory analysis between pet ownership and sleep, exercise, health and neighborhood perceptions : The Whitehall II cohort study

A cross-sectional exploratory analysis between pet ownership and sleep, exercise, health and neighbourhood perceptions: The Whitehall II cohort study Gill Mein (corresponding author), Robert Grant. Faculty of Health, Social Care and Education. Kingston University and St George’s University of London Background: To explore associations between pets, and specifically dog ownership and sleep, health, exercise and neighbourhood. Methods: Cross sectional examination of 6575 participants of the Whitehall II study aged between 59-79 years. We used self-assessed measurement scales of the Short Form (SF36), General Health Questionnaire (GHQ), Control, Autonomy, Self-realisation and Pleasure (CASP), Centre for Epidemiologic Studies Depression Scale (CES-D), sleep, exercise, and perceptions of local neighbourhood. In addition the Mini Mental State Examination which is administered to test global cognitive status (MMSE) Results: We found 2/7 people owned a pet and of those 64% were “very” attached to their pet. Mild exercise in metabolic equivalents (MET-hours) was significantly higher in pet owners than non-owners (median 27.8 (IQR 18.1 to 41.8) vs 25.7 (IQR 16.8 to 38.7), p=0.0001), and in dog owners than other pets (median 32.3 (IQR 20.8 to 46.1) vs 25.6 (IQR 16.8 to 38.5), p<0.0001). Moderate exercise was also significantly higher in pet owners than non pet owners (median 11.8 (IQR 4.2 to 21.9) vs 9.8 (IQR 2.8 to 19.5), p<0.0001), and dog owners than owners of other pets (median 12.3 (IQR 4.2 to 22.2) vs 10.1 (3.1 to 20.0), p=0.0002) but there were no significant differences with vigorous exercise. We found that pet owners were significantly more positive about their neighbourhood than non-owners on 8/9 questions, while dog owners were (significantly) even more positive than owners of other pets on 8/9 questions. Associations with sleep were mixed, although dog owners had less trouble falling asleep than non-dog owners, with borderline statistical significance. Conclusion: Dog owners feel more positive about their neighbourhood, do more exercise, and fall asleep more easily than non-dog owners. These results suggest that dog owners could be more likely to exercise by walking their dogs and therefore may be more familiar and positive about the area in which they walk their dog

Resisting Sleep Pressure:Impact on Resting State Functional Network Connectivity

In today's 24/7 society, sleep restriction is a common phenomenon which leads to increased levels of sleep pressure in daily life. However, the magnitude and extent of impairment of brain functioning due to increased sleep pressure is still not completely understood. Resting state network (RSN) analyses have become increasingly popular because they allow us to investigate brain activity patterns in the absence of a specific task and to identify changes under different levels of vigilance (e.g. due to increased sleep pressure). RSNs are commonly derived from BOLD fMRI signals but studies progressively also employ cerebral blood flow (CBF) signals. To investigate the impact of sleep pressure on RSNs, we examined RSNs of participants under high (19 h awake) and normal (10 h awake) sleep pressure with three imaging modalities (arterial spin labeling, BOLD, pseudo BOLD) while providing confirmation of vigilance states in most conditions. We demonstrated that CBF and pseudo BOLD signals (measured with arterial spin labeling) are suited to derive independent component analysis based RSNs. The spatial map differences of these RSNs were rather small, suggesting a strong biological substrate underlying these networks. Interestingly, increased sleep pressure, namely longer time awake, specifically changed the functional network connectivity (FNC) between RSNs. In summary, all FNCs of the default mode network with any other network or component showed increasing effects as a function of increased 'time awake'. All other FNCs became more anti-correlated with increased 'time awake'. The sensorimotor networks were the only ones who showed a within network change of FNC, namely decreased connectivity as function of 'time awake'. These specific changes of FNC could reflect both compensatory mechanisms aiming to fight sleep as well as a first reduction of consciousness while becoming drowsy. We think that the specific changes observed in functional network connectivity could imply an impairment of information transfer between the affected RSNs

Gene therapy for monogenic liver diseases: clinical successes, current challenges and future prospects

Over the last decade, pioneering liver-directed gene therapy trials for haemophilia B have achieved sustained clinical improvement after a single systemic injection of adeno-associated virus (AAV) derived vectors encoding the human factor IX cDNA. These trials demonstrate the potential of AAV technology to provide long-lasting clinical benefit in the treatment of monogenic liver disorders. Indeed, with more than ten ongoing or planned clinical trials for haemophilia A and B and dozens of trials planned for other inherited genetic/metabolic liver diseases, clinical translation is expanding rapidly. Gene therapy is likely to become an option for routine care of a subset of severe inherited genetic/metabolic liver diseases in the relatively near term. In this review, we aim to summarise the milestones in the development of gene therapy, present the different vector tools and their clinical applications for liver-directed gene therapy. AAV-derived vectors are emerging as the leading candidates for clinical translation of gene delivery to the liver. Therefore, we focus on clinical applications of AAV vectors in providing the most recent update on clinical outcomes of completed and ongoing gene therapy trials and comment on the current challenges that the field is facing for large-scale clinical translation. There is clearly an urgent need for more efficient therapies in many severe monogenic liver disorders, which will require careful risk-benefit analysis for each indication, especially in paediatrics

Aviation Noise Impacts White Paper:State of the Science 2019: Aviation Noise Impacts

This paper provides an overview of the state of the science regarding aviation noise impacts as of early 2019. It contains information on impacts including community noise annoyance, sleep disturbance, health impacts, children’s learning, helicopter noise, supersonic aircraft, urban air mobility and unmanned aerial systems. The paper also considers the economic costs of aviation noise. This information was collected during an ICAO/CAEP Aviation Noise Impacts Workshop in November 2017 and in subsequent follow-on discussions