Abstract
Introduction
Pressure between a CPAP mask and the skin is a significant contributor to irritation and pressure ulcers, an area of localized soft tissue ischemic necrosis caused by prolonged ...pressure over bony prominences that exceeds supra capillary pressure (70 mmHg). We hypothesized that cloth masks (CM) would exert a lower nasal bridge pressure than traditional mask (TM) products constructed of silicone and plastic.
Methods
We evaluated the pressure exerted by seven types of nasal masks in three trials onto the nasal bridge of two healthy adult volunteers, one female, one male, while they received 10 cm H₂O of CPAP. Five commercially available CMs (SleepWeaver® 3D, SleepWeaver® Advance Pediatric, SleepWeaver® Élan, and SleepWeaver® Prevent, Circadiance®, LLC) were tested as were three TMs constructed primarily of silicone and plastic (DreamWisp™, Philips Respironics, Inc.; Mirage™, ResMed; Zest™, Fisher & Paykel Healthcare). Pressure was detected using a texsens®-g low pressure sensor force measuring device. Pressure data from each 30 second trial were summarized as the median value after confirming that pressure did not vary by time (one-way ANOVA, p = 0.7393). Median values were then compared across trials, subjects, and masks using one-way ANOVAs and student’s t-tests.
Results
After confirming that pressure did not vary by trial (one-way ANOVA, p=0.4585) or subject (t-test, p=0.0938), pressure data were summarized by mask. On average, CMs exerted 37.0 (17.7) mmHg of nasal bridge pressure, although there was significant variation across masks (one-way ANOVA, p < 0.0001). Conversely, TMs averaged 112 (38.5) mmHg of nasal bridge pressure without significant variation across masks (one-way ANOVA, p=0.1291). CMs averaged 75.26 mmHg less pressure than TMs (p < 0.0001), a difference of 67 percent.
Conclusion
The data supports the hypothesis that pressure from CMs on the bridge of the nose are significantly lower than a sample of TMs with similar shape and style, and the null hypothesis was rejected. Furthermore, the average CM was below the threshold for capillary closing, in contrast to the average TM. Therefore, for CPAP users with predicted or existing skin sensitivity, comfort and/or compliance concerns, CM should be considered as a first choice in mask selection.
Support (if any):
Abstract
Introduction
Oxytocin is a versatile hypothalamic neuropeptide involved in diverse neurobehavioural processes. Since oxytocin can elicit anxiolytic and serenic effects, one could hypothesise ...that oxytocin should prime the brain for sleep and promote hypnogenesis. However, based on the social salience hypothesis—that oxytocin promotes prosocial behaviour and directs attention toward social stimuli—one could also posit that oxytocin should promote wakefulness. At present, little research has comprehensively characterised the effect of oxytocin on sleep-wake behaviour and no explanation to reconcile these two seemingly competing hypotheses has been proposed.
Methods
This study investigated the effects of oxytocin on sleep-wake outcomes using radiotelemetry-based polysomnography in adult male and female Wistar rats. Oxytocin was administered via the intraperitoneal (IP; 0.1, 0.3 and 1 mg/kg) and intranasal (IN; 0.06, 1, 3 mg/kg) routes. Caffeine (IP and IN; 10 mg/kg) was also administered as a wake-promoting positive control. Additionally, pre-treatment with the oxytocin receptor (OTR) antagonist L-368,899 (IP; 5 mg/kg) and vasopressin 1a receptor (V1aR) antagonist SR49059 (IP; 1 mg/kg) followed by oxytocin (IP; 1 mg/kg) was conducted to determine which receptor(s) mediated sleep-wake effects of oxytocin.
Results
In both male and female rats, IP oxytocin produced dose-dependent effects on sleep-wake behaviour. Specifically, oxytocin initially promoted quiescent wakefulness (a restful but conscious state) at the cost of reducing both active wakefulness and sleep. Throughout the 1.5-hour period post-administration, oxytocin delayed REM sleep onset and reduced the proportion of both NREM and REM sleep. Conversely, IN oxytocin did not significantly alter any sleep-wake parameters at any dose tested. Caffeine demonstrated wake-promoting effects under both the IP and IN routes of administration. The involvement of OTR and V1aR binding in oxytocin-induced effects on sleep-wake outcomes will be discussed.
Conclusion
These findings appear to reconcile the two competing hypotheses: in rats, IP oxytocin appears to promote a state of quiescent wakefulness—one of calm and rest, but also of conscious responsivity to environmental stimuli. IN oxytocin demonstrated little to no effect on sleep-wake behaviour, which is a crucial finding given the escalating use of IN oxytocin as a therapeutic for conditions with comorbid disordered sleep.
Support (if any)
None.
Abstract
Introduction
Our previous study has shown that there is a direct connection between GABAergic neurons in the nucleus pontis oralis (NPO) and neurons of the dorsal raphe nucleus (DR), ...providing a morphological basis for the hypothesis that GABAergic inhibitory processes in NPO play an important role in the generation and maintenance of wakefulness as well as active (REM) sleep through the interaction with neurons in the DR. However, the target of such a GABAergic projection from the NPO within the DR is unknown. In the present study, a double-fluorescent labeling technique was employed to examine the target of GABAergic inputs to the DR.
Methods
Adult cats were deeply anesthetized and perfused transcardially. Subsequently, the brainstem containing the DR was removed, postfixed and cut into 15 μm coronal sections with a Reichert-Jung cryostat. The sections were immunostained with antibodies against GABA-A or GABA-B receptors and GABA following the procedure of double fluorescence immunohistochemistry.
Results
Under fluorescence microscopy, a large number of neurons were labeled with antibodies against either GABA-A receptor or GABA-B receptor. In addition, neurons labeled with antibody against GABA were observed in the DR. With double fluorescence immunohistochemical techniques, some neurons labeled by anti-GABA antibody were also stained with antibodies against GABA-A or GABA-B receptors.
Conclusion
The expression of GABA-A or GABA-B receptors by GABAergic neurons in the DR indicates that GABAergic neurons in the DR receive GABAergic inputs. Our previous study has demonstrated that these GABAergic inputs are from the NPO. These data provide a morphological foundation to support our hypothesis that, during wakefulness, NPO GABAergic “Executive” neurons suppress “Second-Order” GABAergic neurons in the DR, which, in turn, activate (disinhibit) serotonergic wake-on neurons in this nucleus.
Support (if any)
NS092383
The message from medicine is clear. We are in possession of vast amounts of data from sources such as electron microscopes, magnetic resonance imaging and DNA microarray technology. The aim is to ...translate this into a world of faster drug discovery, more accurate automated diagnosis and early warnings of impending disease. Statistics, and in particular statistical inference, has a key role to play in providing a principled approach to this task. In practice, solid theoretical underpinnings are often replaced with heuristics suited only to the data-set in hand. Traditional statistical tools are often ill-equipped to cope with the structure of this new flood of data. The need for methodological improvements presents a major opportunity to progress medical sciences. The scientific method relies on carefully designed experiments, typically collecting N samples each with a small number p of measurements, in order to test a hypothesis or to discover a causal relationship. When p is much smaller than N, existing statistical methods are satisfactory for this purpose. Today, however, the approach is quite different. Extensive quantities of data are available due to the decreasing cost of high throughput measurement devices and data storage alongside rapidly increasing computational power. Examples from biomedicine include genetic and epigenetic data as well as the growing availability of real-time health information from wearable devices and hospital intensive care units. In these cases, the data dimension p can be comparable to the number of samples N. The task is now to look for patterns or correlations in this data without first providing a plausible hypothesis. The response to this problem has been to search for a lower dimensional representation of the data. To achieve this, methods of variable selection, regularization or projection are routinely used. Given its wide-reaching implications for biomedical data studies we examine the phenomenon of overfitting, one of the primary challenges of high-dimensional inference, from two different perspectives: statistical physics in Part I and Bayesian inference in Part II. In the first approach, we consider all variables of the dataset and investigate the inference outcomes in the regime where p is comparable to N. Surprisingly, for a family of models, we have found systematic and reproducible effects which are a function of the ratio p/N.
This thesis examines one particular way in which we might raise awareness among Chinese L2 hearers of the importance of interpreting paralinguistic behaviour and so enhance their pragmatic ...competence. It adopts a cognitive-pragmatic approach to instructed L2 oral comprehension informed by relevance theory and show how exposure to one type of paralinguistic behaviour - prosodic pointing - contributes to the development of increasingly sophisticated interpretive strategies. In Chapter One, I propose that L2 instruction should focus less on teaching 'listening' and more on developing pragmatic competence. This focus entails a multimodal approach to L2 learning and teaching. In Chapter Two, I introduce relevance theory and show how it can accommodate a view which focuses on (i) the hearer's end of interaction and (ii) the role of the speaker's paralinguistic behaviour in the context of fine-tuning L2 hearers' interpretive competence. Chapter Three introduces the type of ostensive paralinguistic behaviour the thesis focuses on: contrastive stress. I account for the comprehension of contrastive stress in relevance-theoretic terms and argue that it is interpreted by virtue of its interaction with co-speech pointing gestures, such as head movements and facial expressions. Adopting a multimodal perspective, I outline a rationale for looking at contrastive stress in its multimodal context: what I call prosodic pointing. I introduce my focus on exposing Chinese L2 hearers to prosodic pointing to develop their ability to infer (dis)agreement. In Chapter Four, I provide a definition of pragmatic competence as ostensiveinferential competence presupposing pragmatic awareness and metapragmatic awareness (Ifantidou, 2014). I highlight my original contribution in focusing on inferential comprehension in L2 hearers and in integrating paralinguistic behaviour (i.e. prosodic pointing) into the Noticing-as-Ostensive model of instruction and formulate my main hypothesis: exposure to prosodic pointing will play an important role in setting the stage for Chinese L2 hearers' recognition of relevance, raising their pragmatic and metapragmatic awareness and improving their pragmatic competence. In Chapter Five, I introduce the intervention study used to test the hypothesis, outlining my methodologies and a mixed methods triangulation research design. Chapter Six presents the data analysis and results of the intervention. Finally, in Chapter Seven, I discuss and interpret the results in the light of the hypothesis and theoretical implications. There is ample evidence of the intervention's effectiveness in enhancing Chinese L2 hearers' ostensive-inferential competence. I also present further evidence that exposure to prosodic pointing is particularly relevant to Chinese L2 hearers.
This thesis contributes to the field of nonparametric hypothesis testing (i.e. two-sample and independence testing) by providing a large-scale framework and developing a Bayesian perspective. We ...focus on nonparametric measures of homogeneity and dependence by considering the Hilbert norms between the embeddings of probability distributions in the reproducing kernel Hilbert space (RKHS). The rich representation provided by the associated kernel feature map enables the use of multivariate or non-Euclidean observations (e.g. strings and graphs) and it leads to powerful tests that are able to solve challenging problems given enough observations. However, the cost of computing the kernel matrix scales at least quadratically in the number of samples and makes it prohibitive to use in modern large-scale datasets. First, we propose three estimators of the well-known kernel dependence measure, the Hilbert Schmidt Independence Criterion (HSIC), namely the block-based estimator, the Nystrom estimator and the random Fourier feature (RFF) estimator, and establish the corresponding linear time independence test for each of the estimators. Secondly, we consider a normalised version of HSIC, the NOrmalised Cross COvariance (NOCCO) statistic, and propose an RFF approximated NOCCO. This results in a distribution free test that is robust to the kernel bandwidth misspecification. Thirdly, we propose a two-step conditional independence test that extends the popular two-step approach REgression with Subsequent Independence Test (RESIT) through RKHS valued regressions. When used as a part of the classical PC algorithm for causal inference, the resulting algorithm is more robust to hidden variables that induce nonfunctional associations. Finally, we utilise the classical Bayes factor formalism for model comparison and propose a Bayesian two-sample test by modelling the witness function of the well-known kernel measure of homogeneity, the Maximum Mean Discrepancy (MMD), with a Gaussian Process.
This thesis investigates the second language (L2) processing and acquisition of English wh-dependencies and definiteness. Two studies were conducted to test whether adult L2 learners can process and ...acquire L2 properties that are not present in their first language (L1). The first study replicates Canales (2012) to compare L2 real-time processing of filler-gap dependencies in English wh-sentences by speakers of two typologically different languages, Jordanian Arabic and Mandarin, which both lack wh-movement. The results show that the L2 participants can process filler-gap dependencies incrementally in real-time and provide evidence that L2 processing exploits the same syntactic knowledge (wh-constraints) as L1 processing. These results challenge the predictions of the Shallow Structure Hypothesis (Clahsen & Felser, 2006, 2018) which states that adult L2 learners are 'shallow processors' who rely less heavily on morpho-syntactic knowledge during real-time processing than on lexical semantic knowledge. The second study investigates the acquisition of definiteness in English relative complementizers by L1 Jordanian speakers. The appearance of relative complementizers in Jordanian Arabic is the phonological reflex of the +definite feature of the head noun, unlike English relative complementizers which are not specified for definiteness. This study examines whether adult L1 Jordanian Arabic L2-English speakers will transfer the +definite feature to English relative complementizers, by investigating their acceptance of null and overt relative complementizers in definite and indefinite English relative clauses. These combinations are all grammatical in English, but in the participants' L1, null complementizers are incompatible with a definite marker and overt complementizers are incompatible with indefiniteness. The results show evidence of L1 transfer since the L2 participants had significantly lower ratings for definite relative clauses with a null complementizer and indefinite relative clauses with an overt relative complementizer. Further, the size of this apparent L1-transfer effect was bigger in participants with lower L2 English proficiency but attenuated with increased proficiency, suggesting that the higher proficiency participants were able to acquire the target representation of definiteness with relative complementizers. These results are compatible with the Feature Reassembly Hypothesis (Lardiere, 2008, 2009) which argues that learners can acquire L2 features that would be incompatible with their L1 features. Overall, the results of both investigations do not support models of L2 processing and acquisition that propose shallower syntactic representation (the Shallow Structure Hypothesis). Instead, they support models which argue that adult L2 learners can acquire full syntactic processing and representation of L2 properties that are absent in their L1 (e.g., the Feature Reassembly Hypothesis).
The primary aim of this thesis is to formulate an intensional definition of aesthetic experience. Its secondary aims are (i) to show how this definition might be used for empirical research and (ii) ...to better understand other terms that are qualified by ‘aesthetic' (chiefly, ‘aesthetic properties' and ‘aesthetic value'). In chapter one, I will explain the nature of the problem we face and why it demands our attention. In chapters two and three, I will critically survey positions in the literature and argue that none adequately characterise aesthetic experience. In chapter four, I will motivate and defend an intensional definition of ‘aesthetic experience' and an art-based account of ‘aesthetic properties'. The former states, put briefly, that aesthetic experiences are those which acquire a valence when the subject attends to the content of her experience for its own sake and discerns aesthetic properties. The latter states that ‘aesthetic properties' are those which comprise the value artworks have as works of art. In chapter five, I will use this definition of aesthetic experience to formulate the hypothesis that mindfulness training can augment one's propensity for having rewarding aesthetic experiences of nature and everyday life. I will then propose how this hypothesis could be empirically investigated. In chapter six, I conclude by examining what my analysis of ‘aesthetic experience' and ‘aesthetic properties' reveals about ‘aesthetic value'. I will then, finally, highlight topics requiring further research.
Syntactic priming is the phenomenon by which the comprehension or production of a given sentence is facilitated by the processing of another sentence with similar or identical syntax. I propose that ...syntactic priming taps into the abstract syntactic representation which incorporates the information on the predicate’s argument structure and thus defend the Argument Structure Priming Hypothesis. This stands in contrast to the widely accepted conceptualisation of syntactic priming, Constituent Structure Priming, where priming concerns mere linear constituent order (Bock & Loebell, 1990). I also argue against the idea of Patient Prominence Priming, where the utterance’s discourse function is assumed to play a role in priming (Vasilyeva & Waterfall, 2012). Seven production priming experiments were conducted with Russian and English adults and 4- to 7-year olds to investigate whether and to what extent these three conceptualisations of syntactic priming are empirically valid. The findings in both languages for both adults and children highlight the significance of argument structure for priming, supporting the Argument Structure Priming Hypothesis, while providing little evidence for Constituent Structure Priming or Patient Prominence Priming. I also explored the Argument Prominence Hierarchy hypothesis (Titov 2012). On this hypothesis the linear order of arguments in a sentence is governed by their relative interpretive status, which is defined by a number of features, animacy being one of them. My findings demonstrate that the participants were sensitive to the animacy distribution in the events they described, exactly as predicted. This allows me to attribute the data in the literature supporting the two alternative conceptualisations of syntactic priming, Constituent Structure Priming and Patient Prominence Priming, to asymmetric distribution of animacy in the experimental items participants described as part of a priming task. Finally, the striking similarity between the syntactic behaviour of adults and children in the present experiments, permits us to sustain the Continuity account of language acquisition.
