Recent Advances in Sensing Oropharyngeal Swallowing Function in Japan

Dysphagia (difficulty in swallowing) is an important issue in the elderly because it causes aspiration pneumonia, which is the second largest cause of death in this group. It also causes decline in activities of daily living and quality of life. The oral phase of swallowing has been neglected, despite its importance in the evaluation of dysphagia, because adequate protocols and measuring devices are unavailable. However, recent advances in sensor technology have enabled straightforward, non-invasive measurement of the movement of important swallowing-related organs such as the lips and tongue, as well as the larynx. In this article, we report the present state and possibility of clinical application of such systems developed in Japan

A review of diet standardization and bolus rheology in the management of dysphagia

PURPOSE OF REVIEW: Texture modification is a widespread practice as a strategy for the management of dysphagia and can be very effective in individual cases. However, it is often performed in a qualitative, subjective manner and practices vary internationally according to multiple sets of national guidelines. This article aims to identify best practice by reviewing the theory and practice of texture modification, focussing on recent advances. RECENT FINDINGS: Instrumental assessment of texture modification in vivo is challenging, and studies including rheology and perception have indicated that fluid viscosity is only one of many factors affecting texture modification in practice. Systematic reviews have identified a historical lack of high-quality clinical evidence, but recent controlled studies are beginning to identify positive and negative aspects of thickened fluids. Research and practice to date have been limited by the lack of control and standardization of foods and drinks. However in 2015 a not-for-profit organization, the International Dysphagia Diet Standardisation Initiative, has published a framework for texture modification from thin liquids to solid foods based on all the existing documentation and guidance, and the - limited - available clinical evidence. SUMMARY: Rheology exists in the lab; however, normal practice is often subjective or lacking control and standardization. In the near future, cohesion of practice and the availability of practical standardization tools may increase awareness and use of rheology

Swallow, breathing and survival: sex-specific effects of opioids.

This dissertation presents a series of studies examining mechanisms of deglutition and respiration, and how these vital processes are impacted by opioids. The experiments in Chapter Two investigated the role of the upper esophagus in airway protection through systematic activation of pharyngeal and esophageal mechanoreceptors in a cat electromyography model. Chapter Three compared effects of opioid administration on breathing and swallowing between male and female rats, and found that females are more susceptible to opioid-induced depression of breathing and swallow than males. Findings from Chapters Two and Three led to the development of a translational model of opioid-induced dysphagia using videofluoroscopy. Chapter Four demonstrated that opioid administration resulted in a significant decline in airway protection during swallow in freely feeding, unrestrained cats. This work has advanced knowledge of the regulation of the upper aerodigestive tract, and its dual roles in breathing and swallowing. An improved understanding of the neural control of deglutition will facilitate the development of effective treatments for dysphagia. This dissertation includes the first study to compare effects of opioids on pharyngeal swallow between sexes, and provides mechanistic and clinically-translatable insights into opioid-induced dysphagia. Elucidating the actions of opioids on the brainstem breathing and swallowing networks will aid the prevention and treatment of opioid-induced respiratory depression and dysphagia related complications such as aspiration pneumonia

Tongue Pressure - A Key Limiting Aspect in Bolus Swallowing

Food oral processing is very basic activity of human life, providing individuals with pleasure, enjoyment and serving their needs for social interaction. Dysphagia describes a disorder affecting the safety and/or efficiency of swallowing. To manage this reduced ability, dysphagic individuals are often prescribed a diet having specific ranges of mechanical properties. As a result, a number of sectors such as food, pharmaceutical and health care industries are eagerly searching for fundamental knowledge in order to design food for vulnerable population. This thesis addresses this gap and aims to investigate the relationship between the mechanical properties of bolus swallowing (e.g. rheology, bolus manipulations, perceived ease / difficult of initiation swallowing and perceived bolus flow behaviour) along with oral pressures (i.e. generated by the tongue) recorded in healthy subjects. This area of oral processing is researched mostly from a clinical point of view and thus knowledge in oral processing from sensory view point is currently limited as shown in the literature review. In this study, some of existing clinical researches were extended using relevant techniques (such as maximum isometric tongue pressure, oral volume and oral residence time). Findings from this thesis demonstrated a strong correlation between sensory perception of bolus (e.g. ease / difficult of swallowing, ease of break-swallow, bolus flow) and subjective measurement of tongue pressure in context of ready-to-swallow food bolus with different rheological properties. Further experiments were conducted to mechanically characterise a range of viscoelastic and pastry food systems and measure the intra-oral pressures applied when breaking these foods. Data analysis showed that a positive correlation existed between tongue strength and oral food handling. From our results, we can conclude that individual’s capacity in tongue pressure generation needs to exceed a certain limit in order to perceive ease in swallowing bolus and also to perceive a bolus flow behaviour. However, such correlation was not seen for individuals with reduced capability in generating MITP. These results support the aim that both the oral physiological conditions (MITP) and the rheological properties of the food (bolus) are important factors that influence the bolus manipulations and comfortable oral handling as well as perceived ease of initiating bolus flow

Understanding the relevance of in-mouth food processing. A review of in vitro techniques

[EN] Oral processing of food is the first step in the eating process. Although the food undergoes a number of changes during mastication that influence the subsequent steps, this stage has very often been neglected in studies of digestion, bioavailability, flavor release, satiety potential, glycemic index determination, etc. The present review draws on different sources such as nutrition, medicine, phoniatry and dentistry to explain some in vitro oral processing methods and techniques that could be transferred to food technology studies to mimic in vivo comminution, insalivation, and bolus formation, describing, as a necessary reference, the respective in vivo physiological processes they attempt to imitate. Developing a deeper understanding of all the aspects of in-mouth process will help food technologists to give this crucial step the necessary attention its due importance and to consider better ways to incorporate it into their studies.The authors wish to acknowledge the financial support of the Spanish Government (project AGL2012-36753-C02) and gratefully acknowledge the financial support of EU FEDER funds. Mary Georgina Hardinge assisted with the translation and corrected the English text.Morell Esteve, P.; Hernando Hernando, MI.; Fiszman, SM. (2014). Understanding the relevance of in-mouth food processing. A review of in vitro techniques. Trends in Food Science and Technology. 35(1):18-31. https://doi.org/10.1016/j.tifs.2013.10.005S183135

Retainer-Free Optopalatographic Device Design and Evaluation as a Feedback Tool in Post-Stroke Speech and Swallowing Therapy

Stroke is one of the leading causes of long-term motor disability, including oro-facial impairments which affect speech and swallowing. Over the last decades, rehabilitation programs have evolved from utilizing mainly compensatory measures to focusing on recovering lost function. In the continuing effort to improve recovery, the concept of biofeedback has increasingly been leveraged to enhance self-efficacy, motivation and engagement during training. Although both speech and swallowing disturbances resulting from oro-facial impairments are frequent sequelae of stroke, efforts to develop sensing technologies that provide comprehensive and quantitative feedback on articulator kinematics and kinetics, especially those of the tongue, and specifically during post-stroke speech and swallowing therapy have been sparse. To that end, such a sensing device needs to accurately capture intraoral tongue motion and contact with the hard palate, which can then be translated into an appropriate form of feedback, without affecting tongue motion itself and while still being light-weight and portable. This dissertation proposes the use of an intraoral sensing principle known as optopalatography to provide such feedback while also exploring the design of optopalatographic devices itself for use in dysphagia and dysarthria therapy. Additionally, it presents an alternative means of holding the device in place inside the oral cavity with a newly developed palatal adhesive instead of relying on dental retainers, which previously limited device usage to a single person. The evaluation was performed on the task of automatically classifying different functional tongue exercises from one another with application in dysphagia therapy, whereas a phoneme recognition task was conducted with application in dysarthria therapy. Results on the palatal adhesive suggest that it is indeed a valid alternative to dental retainers when device residence time inside the oral cavity is limited to several tens of minutes per session, which is the case for dysphagia and dysarthria therapy. Functional tongue exercises were classified with approximately 61 % accuracy across subjects, whereas for the phoneme recognition task, tense vowels had the highest recognition rate, followed by lax vowels and consonants. In summary, retainer-free optopalatography has the potential to become a viable method for providing real-time feedback on tongue movements inside the oral cavity, but still requires further improvements as outlined in the remarks on future development.:1 Introduction 1.1 Motivation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1.2 Problem statement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 1.3 Goals and contributions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 1.4 Scope and limitations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 2 Basics of post-stroke speech and swallowing therapy 2.1 Dysarthria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 2.2 Dysphagia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 2.3 Treatment rationale and potential of biofeedback . . . . . . . . . . . . . . . . . 13 2.4 Summary and conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 3 Tongue motion sensing 3.1 Contact-based methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 3.1.1 Electropalatography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 3.1.2 Manometry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 3.1.3 Capacitive . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 3.2 Non-contact based methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 3.2.1 Electromagnetic articulography . . . . . . . . . . . . . . . . . . . . . . . 23 3.2.2 Permanent magnetic articulography . . . . . . . . . . . . . . . . . . . . 24 3.2.3 Optopalatography (related work) . . . . . . . . . . . . . . . . . . . . . . 25 3.3 Electro-optical stomatography . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 3.4 Extraoral sensing techniques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 3.5 Summary, comparison and conclusion . . . . . . . . . . . . . . . . . . . . . . . 29 4 Fundamentals of optopalatography 4.1 Important radiometric quantities . . . . . . . . . . . . . . . . . . . . . . . . . . 32 4.1.1 Solid angle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32 4.1.2 Radiant flux and radiant intensity . . . . . . . . . . . . . . . . . . . . . 33 4.1.3 Irradiance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 4.1.4 Radiance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 4.2 Sensing principle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34 4.2.1 Analytical models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 4.2.2 Monte Carlo ray tracing methods . . . . . . . . . . . . . . . . . . . . . . 37 4.2.3 Data-driven models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38 4.2.4 Model comparison . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39 4.3 A priori device design consideration . . . . . . . . . . . . . . . . . . . . . . . . 41 4.3.1 Optoelectronic components . . . . . . . . . . . . . . . . . . . . . . . . . 41 4.3.2 Additional electrical components and requirements . . . . . . . . . . . . 43 4.3.3 Intraoral sensor layout . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44 5 Intraoral device anchorage 5.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 5.1.1 Mucoadhesion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46 5.1.2 Considerations for the palatal adhesive . . . . . . . . . . . . . . . . . . . 48 5.2 Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48 5.2.1 Polymer selection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48 5.2.2 Fabrication method . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 5.2.3 Formulations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50 5.2.4 PEO tablets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50 5.2.5 Connection to the intraoral sensor’s encapsulation . . . . . . . . . . . . 50 5.2.6 Formulation evaluation . . . . . . . . . . . . . . . . . . . . . . . . . . . 51 5.3 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54 5.3.1 Initial formulation evaluation . . . . . . . . . . . . . . . . . . . . . . . . 54 5.3.2 Final OPG adhesive formulation . . . . . . . . . . . . . . . . . . . . . . 56 5.4 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57 6 Initial device design with application in dysphagia therapy 6.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58 6.2 Optode and optical sensor selection . . . . . . . . . . . . . . . . . . . . . . . . . 60 6.2.1 Optode and optical sensor evaluation procedure . . . . . . . . . . . . . . 61 6.2.2 Selected optical sensor characterization . . . . . . . . . . . . . . . . . . 62 6.2.3 Mapping from counts to millimeter . . . . . . . . . . . . . . . . . . . . . 62 6.2.4 Results and discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62 6.3 Device design and hardware implementation . . . . . . . . . . . . . . . . . . . . 64 6.3.1 Block diagram . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64 6.3.2 Optode placement and circuit board dimensions . . . . . . . . . . . . . 64 6.3.3 Firmware description and measurement cycle . . . . . . . . . . . . . . . 66 6.3.4 Encapsulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 6.3.5 Fully assembled OPG device . . . . . . . . . . . . . . . . . . . . . . . . 67 6.4 Evaluation on the gesture recognition task . . . . . . . . . . . . . . . . . . . . . 69 6.4.1 Exercise selection, setup and recording . . . . . . . . . . . . . . . . . . . 69 6.4.2 Data corpus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70 6.4.3 Sequence pre-processing . . . . . . . . . . . . . . . . . . . . . . . . . . . 70 6.4.4 Choice of classifier . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71 6.4.5 Training and evaluation . . . . . . . . . . . . . . . . . . . . . . . . . . . 72 6.4.6 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73 6.5 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74 7 Improved device design with application in dysarthria therapy 7.1 Device design . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79 7.1.1 Design considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80 7.1.2 General system overview . . . . . . . . . . . . . . . . . . . . . . . . . . . 81 7.1.3 Intraoral sensor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81 7.1.4 Receiver and controller . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82 7.1.5 Multiplexer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85 7.2 Hardware implementation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87 7.2.1 Optode placement and circuit board layout . . . . . . . . . . . . . . . . 87 7.2.2 Encapsulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89 7.3 Device characterization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90 7.3.1 Photodiode transient response . . . . . . . . . . . . . . . . . . . . . . . 91 7.3.2 Current source and rise time . . . . . . . . . . . . . . . . . . . . . . . . 91 7.3.3 Multiplexer switching speed . . . . . . . . . . . . . . . . . . . . . . . . . 92 7.3.4 Measurement cycle and firmware implementation . . . . . . . . . . . . . 93 7.3.5 In vitro measurement accuracy . . . . . . . . . . . . . . . . . . . . . . . 95 7.3.6 Optode measurement stability . . . . . . . . . . . . . . . . . . . . . . . 96 7.4 Evaluation on the phoneme recognition task . . . . . . . . . . . . . . . . . . . . 98 7.4.1 Corpus selection and recording setup . . . . . . . . . . . . . . . . . . . . 98 7.4.2 Annotation and sensor data post-processing . . . . . . . . . . . . . . . . 98 7.4.3 Mapping from counts to millimeter . . . . . . . . . . . . . . . . . . . . . 99 7.4.4 Classifier and feature selection . . . . . . . . . . . . . . . . . . . . . . . 100 7.4.5 Evaluation paradigms . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103 7.5 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105 7.5.1 Tongue distance curve prediction . . . . . . . . . . . . . . . . . . . . . . 105 7.5.2 Tongue contact patterns and contours . . . . . . . . . . . . . . . . . . . 105 7.5.3 Phoneme recognition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 106 7.6 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108 8 Conclusion and future work 115 9 Appendix 9.1 Analytical light transport models . . . . . . . . . . . . . . . . . . . . . . . . . . 119 9.2 Meshed Monte Carlo method . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120 9.3 Laser safety . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122 9.4 Current source modulation voltage . . . . . . . . . . . . . . . . . . . . . . . . . 123 9.5 Transimpedance amplifier’s frequency responses . . . . . . . . . . . . . . . . . . 123 9.6 Initial OPG device’s PCB layout and circuit diagrams . . . . . . . . . . . . . . 127 9.7 Improved OPG device’s PCB layout and circuit diagrams . . . . . . . . . . . . 129 9.8 Test station layout drawing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138 Bibliography 152Der Schlaganfall ist eine der häufigsten Ursachen für motorische Langzeitbehinderungen, einschließlich solcher im Mund- und Gesichtsbereich, deren Folgen u.a. Sprech- und Schluckprobleme beinhalten, welche sich in den beiden Symptomen Dysarthrie und Dysphagie äußern. In den letzten Jahrzehnten haben sich Rehabilitationsprogramme für die Behandlung von motorisch ausgeprägten Schlaganfallsymptomatiken substantiell weiterentwickelt. So liegt nicht mehr die reine Kompensation von verlorengegangener motorischer Funktionalität im Vordergrund, sondern deren aktive Wiederherstellung. Dabei hat u.a. die Verwendung von sogenanntem Biofeedback vermehrt Einzug in die Therapie erhalten, um Motivation, Engagement und Selbstwahrnehmung von ansonsten unbewussten Bewegungsabläufen seitens der Patienten zu fördern. Obwohl jedoch Sprech- und Schluckstörungen eine der häufigsten Folgen eines Schlaganfalls darstellen, wird diese Tatsache nicht von der aktuellen Entwicklung neuer Geräte und Messmethoden für quantitatives und umfassendes Biofeedback reflektiert, insbesondere nicht für die explizite Erfassung intraoraler Zungenkinematik und -kinetik und für den Anwendungsfall in der Schlaganfalltherapie. Ein möglicher Grund dafür liegt in den sehr strikten Anforderungen an ein solche Messmethode: Sie muss neben Portabilität idealerweise sowohl den Kontakt zwischen der Zunge und dem Gaumen, als auch die dreidimensionale Bewegung der Zunge in der Mundhöhle erfassen, ohne dabei die Artikulation selbst zu beeinflussen. Um diesen Anforderungen gerecht zu werden, wird in dieser Dissertation das Messprinzip der Optopalatographie untersucht, mit dem Schwerpunkt auf der Anwendung in der Dysarthrie- und Dysphagietherapie. Dies beinhaltet auch die Entwicklung eines entsprechenden Gerätes sowie dessen Befestigungsmethode in der Mundhöhle über ein dediziertes Mundschleimhautadhäsiv. Letzteres umgeht das bisherige Problem der notwendigen Anpassung eines solchen intraoralen Gerätes an einen einzelnen Nutzer. Für die Anwendung in der Dysphagietherapie erfolgte die Evaluation anhand einer automatischen Erkennung von Mobilisationsübungen der Zunge, welche routinemäßig in der funktionalen Dysphagietherapie durchgeführt werden. Für die Anwendung in der Dysarthrietherapie wurde eine Lauterkennung durchgeführt. Die Resultate bezüglich der Verwendung des Mundschleimhautadhäsives suggerieren, dass dieses tatsächlich eine valide Alternative zu den bisher verwendeten Techniken zur Befestigung intraoraler Geräte in der Mundhöhle darstellt. Zungenmobilisationsübungen wurden über Probanden hinweg mit einer Rate von 61 % erkannt, wogegen in der Lauterkennung Langvokale die höchste Erkennungsrate erzielten, gefolgt von Kurzvokalen und Konsonanten. Zusammenfassend lässt sich konstatieren, dass das Prinzip der Optopalatographie eine ernstzunehmende Option für die intraorale Erfassung von Zungenbewegungen darstellt, wobei weitere Entwicklungsschritte notwendig sind, welche im Ausblick zusammengefasst sind.:1 Introduction 1.1 Motivation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1.2 Problem statement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 1.3 Goals and contributions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 1.4 Scope and limitations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 2 Basics of post-stroke speech and swallowing therapy 2.1 Dysarthria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 2.2 Dysphagia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 2.3 Treatment rationale and potential of biofeedback . . . . . . . . . . . . . . . . . 13 2.4 Summary and conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 3 Tongue motion sensing 3.1 Contact-based methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 3.1.1 Electropalatography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 3.1.2 Manometry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 3.1.3 Capacitive . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 3.2 Non-contact based methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 3.2.1 Electromagnetic articulography . . . . . . . . . . . . . . . . . . . . . . . 23 3.2.2 Permanent magnetic articulography . . . . . . . . . . . . . . . . . . . . 24 3.2.3 Optopalatography (related work) . . . . . . . . . . . . . . . . . . . . . . 25 3.3 Electro-optical stomatography . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 3.4 Extraoral sensing techniques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 3.5 Summary, comparison and conclusion . . . . . . . . . . . . . . . . . . . . . . . 29 4 Fundamentals of optopalatography 4.1 Important radiometric quantities . . . . . . . . . . . . . . . . . . . . . . . . . . 32 4.1.1 Solid angle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32 4.1.2 Radiant flux and radiant intensity . . . . . . . . . . . . . . . . . . . . . 33 4.1.3 Irradiance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 4.1.4 Radiance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 4.2 Sensing principle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34 4.2.1 Analytical models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 4.2.2 Monte Carlo ray tracing methods . . . . . . . . . . . . . . . . . . . . . . 37 4.2.3 Data-driven models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38 4.2.4 Model comparison . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39 4.3 A priori device design consideration . . . . . . . . . . . . . . . . . . . . . . . . 41 4.3.1 Optoelectronic components . . . . . . . . . . . . . . . . . . . . . . . . . 41 4.3.2 Additional electrical components and requirements . . . . . . . . . . . . 43 4.3.3 Intraoral sensor layout . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44 5 Intraoral device anchorage 5.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 5.1.1 Mucoadhesion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46 5.1.2 Considerations for the palatal adhesive . . . . . . . . . . . . . . . . . . . 48 5.2 Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48 5.2.1 Polymer selection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48 5.2.2 Fabrication method . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 5.2.3 Formulations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50 5.2.4 PEO tablets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50 5.2.5 Connection to the intraoral sensor’s encapsulation . . . . . . . . . . . . 50 5.2.6 Formulation evaluation . . . . . . . . . . . . . . . . . . . . . . . . . . . 51 5.3 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54 5.3.1 Initial formulation evaluation . . . . . . . . . . . . . . . . . . . . . . . . 54 5.3.2 Final OPG adhesive formulation . . . . . . . . . . . . . . . . . . . . . . 56 5.4 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57 6 Initial device design with application in dysphagia therapy 6.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58 6.2 Optode and optical sensor selection . . . . . . . . . . . . . . . . . . . . . . . . . 60 6.2.1 Optode and optical sensor evaluation procedure . . . . . . . . . . . . . . 61 6.2.2 Selected optical sensor characterization . . . . . . . . . . . . . . . . . . 62 6.2.3 Mapping from counts to millimeter . . . . . . . . . . . . . . . . . . . . . 62 6.2.4 Results and discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62 6.3 Device design and hardware implementation . . . . . . . . . . . . . . . . . . . . 64 6.3.1 Block diagram . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64 6.3.2 Optode placement and circuit board dimensions . . . . . . . . . . . . . 64 6.3.3 Firmware description and measurement cycle . . . . . . . . . . . . . . . 66 6.3.4 Encapsulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 6.3.5 Fully assembled OPG device . . . . . . . . . . . . . . . . . . . . . . . . 67 6.4 Evaluation on the gesture recognition task . . . . . . . . . . . . . . . . . . . . . 69 6.4.1 Exercise selection, setup and recording . . . . . . . . . . . . . . . . . . . 69 6.4.2 Data corpus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70 6.4.3 Sequence pre-processing . . . . . . . . . . . . . . . . . . . . . . . . . . . 70 6.4.4 Choice of classifier . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71 6.4.5 Training and evaluation . . . . . . . . . . . . . . . . . . . . . . . . . . . 72 6.4.6 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73 6.5 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74 7 Improved device design with application in dysarthria therapy 7.1 Device design . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79 7.1.1 Design considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80 7.1.2 General system overview . . . . . . . . . . . . . . . . . . . . . . . . . . . 81 7.1.3 Intraoral sensor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81 7.1.4 Receiver and controller . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82 7.1.5 Multiplexer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85 7.2 Hardware implementation . . . . . . . . . . . . . . . . . . . . .

Patient Responses To Swallowing Safety Cues: A Comparison Of Traditional Face-to-Face And Tele-Dysphagia Instructional Methods

An estimated 15 million individuals in the United States have been formally diagnosed with dysphagia, defined as swallowing dysfunction -- the fifth leading cause of death in Americans over the age of 65. Statistical findings indicate that at least 50% of these individuals have limited access to treatment. However, despite the rapid expansion of telepractice (defined as the use of telecommunications technology to provide services at a distance) as a statistically valid online method for the provision of medical and clinical intervention to those without access, telepractice has yet to consistently incorporate online dysphagia service delivery (referred to as tele-dysphagia) into its clinical scope. This investigation compared the outcomes of traditional face-to-face intervention to online tele-dysphagia intervention by measuring the correct and incorrect responses to visual and auditory cues presented by a clinician during dysphagia intervention sessions. Data analysis conducted via t-test indicated that there was no significant difference in the mean scores from tele-dysphagia method (M = 9.67, SD = 3.74) as compared to face-to-face method (M = 9.00, SD = 2.70), t (28) = - 0.56, p = 0.580. Additionally, inter-rater reliability scores were obtained by determining a Cohen’s kappa coefficient in order to measure the degree of agreement between the two raters. Findings indicated a kappa statistic of k=1 for all items, given a 100% agreement for all trials. Additionally, results of a mixed-design analysis of variance suggested a significant within-subject effect with the use of cues, but there were no significant main effects of between-subject factors (gender, delivery type, etiology, or age) on the patients’ responses. Given that there was no significant statistical difference between the two delivery methods and inter-rater reliability scores demonstrated perfect agreement, we can suggest that the online tele-dysphagia method can potentially yield clinical outcomes similar to a traditional face-to-face method. Results from a mixed-design analysis of variance additionally suggested that there is a significant within-subject effect given the use of cues (F (1, 29)=14.99, p = .001) on patients’ responses. However, there were no significant main effects of between-subject factors (gender, delivery type, etiology, or age) on the patients’ responses. It is hoped that the results of this study will lend validity and direction to future attempts to provide much-needed dysphagia intervention via online service methods. Such attempts, in turn, would have the potential to promote increased longevity and quality of life in those populations currently unable to access such services

Intravital Imaging in a Zebrafish Model Elucidates Interactions Between Mucosal Immunity and Pathogenic Fungi

Candida yeasts are common commensals that can cause mucosal disease and life-threatening systemic infections. While many of the components required for defense against Candida albicans infection are well established, questions remain about how various host cells at mucosal sites assess threats and coordinate defenses to prevent normally commensal organisms from becoming pathogenic. Using two Candida species, C. albicans and C. parapsilosis, which differ in their abilities to damage epithelial tissues, we used traditional methods (pathogen CFU, host survival, and host cytokine expression) combined with high-resolution intravital imaging of transparent zebrafish larvae to illuminate host-pathogen interactions at the cellular level in the complex environment of a mucosal infection. In zebrafish, C. albicans grows as both yeast and epithelium-damaging filaments, activates the NF-kB pathway, evokes proinflammatory cytokines, and causes the recruitment of phagocytic immune cells. On the other hand, C. parapsilosis remains in yeast morphology and elicits the recruitment of phagocytes without inducing inflammation. High-resolution mapping of phagocyte-Candida interactions at the infection site revealed that neutrophils and macrophages attack both Candida species, regardless of the cytokine environment. Time-lapse monitoring of single-cell gene expression in transgenic reporter zebrafish revealed a partitioning of the immune response during C. albicans infection: the transcription factor NF-kB is activated largely in cells of the swimbladder epithelium, while the proinflammatory cytokine tumor necrosis factor alpha (TNF-a) is expressed in motile cells, mainly macrophages. Our results point to different host strategies for combatting pathogenic Candida species and separate signaling roles for host cell types

Demethylation Therapy As A Novel Treatment For Human Papilloma Virus-Associated Head And Neck Cancer

5-azacytidine (5-aza) and its structural analog 5-aza-2’-deoxycytidine (decitabine) are demethylating agents currently used to treat myelodysplastic syndrome and acute myeloid leukemia. In addition to demethylating DNA, they are known to cause DNA damage and activate DNA damage response pathways, but our mechanistic understanding of these processes is incomplete. Given the unique epigenetic profile of human papilloma virus-associated (HPV+) head and neck squamous cell carcinoma (HNSCC), we sought to develop demethylation therapy as a novel, targeted treatment for this subset of cancer that has less morbidity than current treatments. We wanted to characterize the DNA damage and describe the mechanism of damage induced by 5-aza in these cells, as well as the cellular response and effect on metastatic potential in cells, xenograft models, and tumors from patients treated in a clinical trial at the Yale Cancer Center. By using pulsed-field gel electrophoresis, we found that demethylation treatment induces DNA double strand break formation exclusively in HPV+ head and neck cancer cells, and that these breaks depend on active transcription, replication, and expression of a known antiviral enzyme, apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3 (APOBEC3B). Furthermore, we found that demethylation therapy also reactivates p53, downregulates HPV genes, reduces the expression of matrix metalloproteinases, and reduces the metastatic potential in cells, xenograft models, and in patient tumors