Book Summary: This book comprehensively covers the assessment and treatment of balance system impairments. Designed to be used in graduate programs in audiology, and by practicing audiologists, it is also appropriate for those in the fields of physical therapy, otolaryngology, and neurology. Assessment chapters address ocular motility testing, positional/positioning testing, caloric testing, rotational testing, computerized dynamic posturography, and vestibular evoked potentials. Treatment chapters cover non-medical, medical, and surgical treatment of dizziness and vertigo, vestibular rehabilitation and assessment of and intervention for falls risk. Additionally, the book provides background information on the vestibular and ocular motor systems, sample cases, and a final chapter, "Putting It All Together."

In Darwinian evolution, a living population evolves when it is exposed to the selection pressures of a new biological medium. Analogously, in my chromatic evolution a chord "evolves" when it is exposed to a new chromatic medium, forcing it to adapt and harmonically modify its pitch content. This is a process by which a diatonic, consonant chord is progressively transformed into a chromatic substitute, over a span of several similar works, without losing or modifying the chord’s resolution tendencies, harmonic function, or formal location. From a Schenkerian perspective—and using Felix Mendelssohn’s Songs without Words as my corpus study—I will demonstrate how the pre-recapitulatory dominant (the root-position dominant that conventionally precedes the recapitulation) progressively evolves into a highly chromatic substitute: the dominant of the mediant.

The ATP-gated P2X7 receptor (P2X7R) is a non-selective cation channel which senses high extracellular ATP concentrations and has been suggested as a target for the treatment of neuroinflammation and neurodegenerative diseases. The use of P2X7R antagonists may therefore be a viable approach for treating CNS pathologies, including epileptic disorders. Recent studies showed anticonvulsant potential of P2X7R antagonists in certain animal models. To extend this work, we tested three CNS-permeable P2X7R blocker (Brilliant Blue G, AFC-5128, JNJ-47965567) and a natural compound derivative (tanshinone IIA sulfonate) in four well-characterized animal seizure models. In the maximal electroshock seizure threshold test and the pentylenetetrazol (PTZ) seizure threshold test in mice, none of the four compounds demonstrated anticonvulsant effects when given alone. Notably, in combination with carbamazepine, both AFC-5128 and JNJ-47965567 increased the threshold in the maximal electroshock seizure test. In the PTZ-kindling model in rats, useful for testing antiepileptogenic activities, Brilliant Blue G and tanshinone exhibited a moderate retarding effect, whereas the potent P2X7R blocker AFC-5128 and JNJ-47965567 showed a significant and long-lasting delay in kindling development. In fully kindled rats, the investigated compounds revealed modest effects to reduce the mean seizure stage. Furthermore, AFC-5128- and JNJ-47965567-treated animals displayed strongly reduced Iba 1 and GFAP immunoreactivity in the hippocampal CA3 region. In summary, our results show that P2X7R antagonists possess no remarkable anticonvulsant effects in the used acute screening tests, but can attenuate chemically-induced kindling. Further studies would be of interest to support the concept that P2X7R signalling plays a crucial role in the pathogenesis of epileptic disorders.

Thesis (MMus (Music)) -- Stellenbosch University, 2010. / ENGLISH ABSTRACT: The purpose of the present study is twofold: I. In the first instance, it is aimed at promoting a better acquaintance with and a deeper understanding of the generally less well-known solmisation systems that have emerged within the oriental music sphere. In this regard a general definition of solmisation is provided, followed by a historic overview of indigenous solmisation systems that have been developed in China, Korea, Japan, India, Indonesia and the Arab world, thereby also confirming the status of solmisation as a truly global phenomenon. II. The second objective of the study was to investigate the current use of solmisation, and the Tonic Sol-fa system in particular, in aural training at South African universities. In order to achieve this, an inquiry was conducted by means of a survey which consisted of (a) a survey questionnaire that was sent to designers/instructors/coordinators of aural training modules at relevant South African universities and (b) additional correspondence that was subsequently undertaken with some of these respondents. This was done with the aim of obtaining information regarding the following: (1) the extent to which solmisation is still being employed in this context; (2) which solmisation systems or alternative approaches to solmisation are being used; (3) what the respondents’ personal motivations are for employing or not employing solmisation; (4) what instruction material is being utilised in either regard; and (5) what the respondents’ personal views are regarding the use of solmisation in aural training. The outcome of the survey confirmed that solmisation, and the Tonic Sol-fa system in particular, is still actively being used in aural training at South African universities, while at the same time providing some insight into the general application thereof in this context. On the whole, the survey also affirmed the continued relevance of solmisation, and the Tonic Sol-fa system in particular, both in the broader South African context and specifically within the context of aural training at South African universities, showing that solmisation continues to be regarded as a valuable aid in the instruction of aural training by the majority of the designers/instructors/coordinators of aural training modules that participated in the survey. / AFRIKAANSE OPSOMMING: Die doel van die onderhawige studie is tweeledig van aard: I. In die eerste plek is dit gemik op die bevordering van beter vertroudheid met en ’n grondiger begrip van die oor die algemeen minder bekende solmisasiestelsels wat binne die konteks van oosterse musiek na vore getree het. In hierdie verband word daar ’n algemene omskrywing van solmisasie voorsien, gevolg deur ’n historiese oorsig oor inheemse solmisasiestelsels wat ontwikkel is in China, Korea, Japan, Indië, Indonesië en die Arabiese wêreld, en word die status van solmisasie as ’n wesenlik wêreldwye verskynsel dan ook daardeur bevestig. II. Die tweede doelwit van die studie was om ondersoek in te stel na die huidige gebruik van solmisasie, en die Tonic Sol-fa stelsel in besonder, in gehooropleiding aan Suid-Afrikaanse universiteite. Om dit te bewerkstellig, is ’n ondersoek uitgevoer deur middel van ’n opname wat bestaan het uit (a) ’n opnamevraelys wat gestuur is aan opstellers/dosente/koördineerders van gehoorlopleidingsmodules aan relevante Suid-Afrikaanse universiteite en (b) bykomende korrespondensie wat daaropvolgend onderneem is met van hierdie respondente. Dit is gedoen met die doel om inligting te bekom rakende die volgende: (1) die mate waarin solmisasie nog binne hierdie konteks gebruik word; (2) watter solmisasiestelsels of alternatiewe benaderings vir solmisasie gebruik word; (3) wat die respondente se persoonlike motiverings is vir die gebruik van solmisasie al dan nie; (4) watter onderrigmateriaal daar in beide gevalle gebruik word; en (5) wat die respondente se persoonlike sieninge is ten opsigte van die gebruik van solmisasie in gehooropleiding. Die uitslag van die opname het bevestig dat solmisasie, en die Tonic Sol-fa stelsel in besonder, steeds aktief gebruik word in gehooropleiding aan Suid-Afrikaanse universiteite, en het terselfdertyd insig gebied in die algemene aanwending daarvan binne hierdie konteks. In sy geheel het die uitslag van die opname dan ook die voortgesette relevansie van solmisasie, en die Tonic Sol-fa stelsel in besonder, in die breër Suid-Afrikaanse konteks sowel as spesifiek binne die konteks van gehooropleiding aan Suid-Afrikaanse universiteite bevestig, en het dit aangetoon dat solmisasie steeds as ’n waardevolle hulpmiddel in die onderrig van gehooropleiding beskou word deur die meeste van die opstellers/dosente/koördineerders van gehoorlopleidingsmodules wat aan die opname deelgeneem het.

De nombreuses études ont montré une modification de la perception de la douleur au cours du vieillissement. Cette modification s’exprime principalement par une diminution du seuil de la douleur aiguë et une augmentation de la prévalence de douleurs chroniques. Parallèlement, le vieillissement provoque des altérations cérébrales importantes, notamment dans les réseaux frontaux. Dans ce travail de thèse, nous avons étudié les mécanismes centraux, notamment les fonctions des réseaux frontaux sur la perception et la modulation de la douleur chez la personne âgée. Les résultats des expériences 1 à 3 suggèrent une forte corrélation positive entre l’altération des fonctions exécutives et le déclin de la modulation cognitive de la douleur et de la résistance à la douleur tonique. Dans l’expérience 4, nos résultats montrent que les scores aux tests mesurant les fonctions émotionnelles (e.g. la reconnaissance des émotions) sont corrélés au ressenti de la douleur. Cela pourrait indiquer un déficit chez les personnes âgées de la composante émotionnelle qui entre en jeu dans la perception de la douleur. / Age-related changes in pain perception have been widely reported in the literature, showing a reduced acute pain perception and an increased prevalence of chronic pain. Ageing also results in considerable alterations in brain structures and functions, particularly in frontal networks. In this thesis, we explored the underlying central mechanisms, especially the role of frontal functions in the age-related alterations in pain perception. Results of experiments 1-3 demonstrated a strong positive correlation between the age-related alterations in executive function and the decline in pain tolerance and cognitive pain modulation. In experiment 4 we observed that the emotional function measured by a test of emotions recognition was correlated to the verbal expression of perceived pain, indicating that the reduced pain expression in the elderly may result from the deficient responses to emotion.

L’évaluation de biomarqueurs et de thérapies innovantes pour la maladie d’Alzheimer (MA) souffre de la mauvaise compréhension des phases initiales de la maladie mais également du manque de modèles animaux pertinents et proches de la physiopathologie humaine. La majorité des modèles rongeurs disponibles reproduisent en seulement quelques mois les lésions classiques de la MA telles que les plaques amyloïdes et les dégénérescences neurofibrillaires (DNF), alors que leur apparition prend des années chez l’Homme. L’objectif de mon travail de doctorat a été de développer une nouvelle stratégie de modélisation des phases précoces de la MA sans surexpression majeure de transgène. Pour cela, nous avons utilisé le co-transfert des gènes humains APPSL et PS1M146L à l’aide de vecteurs viraux dans l’hippocampe de souris et de rats de 8 semaines. Nous avons caractérisé ces modèles et montré une production de peptides, comme le betaCTF ou l’abeta?42 issus du clivage de l’APP, similaire à ce que l’on observe dans l’hippocampe de patients atteints de la MA. Nous avons également montré une hyperphosphorylation de Tau et une défaillance synaptique caractérisée par une diminution des niveaux de PSD-95 et GLT-1 ainsi que par une augmentation du courant tonique glutamatergique. Ces modifications ont enfin été associées à des défauts comportementaux. Mes résultats suggèrent que de nombreux évènements apparaissent bien avant la formation des plaques amyloïdes ou des DNFs et conduisent à une perturbation de la synapse et à l’apparition précoce de défauts comportementaux. Nous disposons donc d’outils relevants quant à la compréhension des premiers stades de la MA qui permettront à la fois de tester de nouveaux composés médicaments sur ces modèles à large fenêtre thérapeutique, et de découvrir de nouveaux biomarqueurs précoces dans le plasma et le liquide cérébro-spinal. / Evaluation of biomarkers and new innovative therapies for Alzheimer's disease (AD) suffers from a misunderstanding of early phases and lack of appropriate animal models close to the human physiopathology. Most available rodent models reproduce hallmarks of AD such as amyloid plaques and neurofibrillary tangles in a few months, while it takes many years to be achieved in human. My PhD work consisted to develop a new modelling strategy of AD early phases without major overexpression of transgenes. To do so, we used gene transfer of human APPSL and PS1M146L using viral vectors injection in the hippocampus of 8 weeks old mice and rats. We characterized these models and showed peptides production, such as betaCTF and abeta42 from APP processing, similar to what is observed in AD patients hippocampi. We also highlighted a hyperphosphorylation of Tau followed by a synaptic failure characterized by a decrease of PSD-95 and GLT-1 levels and by an increase of the tonic current mediated by glutamate. These changes have been finally associated with behavioral deficits. My results suggest that many events appear well before the formation of amyloid plaques or tangles and lead to the disruption of the synapse and the early onset of behavioral defects. Thus, we now have relevant tools to understand the early stages of AD, which will allow us to test new drug compounds on these models with a wide therapeutic window and discover new early biomarkers in plasma and cerebrospinal fluid.

No description available.

Virtual reality (VR) has become an important tool in the study of human balance. It has also been used as a training tool for seated balance and assistive mobility devices. The objective was to design a system that can be used to investigate the effect of VR on trunk muscles during perturbed sitting and perform a preliminary study with two subjects. A spherical system was designed that rotated 26º in the pitch and roll plane at three speeds. The corresponding muscle activity was recorded using EMG in the presence and absence of VR during perturbed sitting. The design was capable of performing the required motions. The results showed a maximum of 31.8% and a minimum of 3.66% muscle activity, relative to maximum voluntary contraction. Our findings suggested that our developed system was successfully able to detect a noticeable effect of VR under perturbed sitting on the subjects’ EMG responses.

While prolonged nearwork is considered to be an environmental risk factor associated with myopia development, an underlying genetic susceptibility to nearwork-induced accommodative adaptation may be one possible mechanism for human myopia development. As the control of accommodation by the autonomic system may be one such genetically predetermined system, this research sought to investigate whether an anomaly of the autonomic control of accommodation may be responsible for myopia development and progression. The emphasis of this work was determining the effect of altering the sympathetic input to the ciliary muscle on accommodation responses such as tonic accommodation and nearwork-induced accommodative adaptation in myopes and non-myopes. The first study of the thesis was based on observations of Gilmartin and Winfield (1995) which suggested that a deficit in the sympathetic inputs to the ciliary muscle may be associated with a propensity for myopia development. The effect of ß-antagonism with timolol application on accommodation characteristics was studied in different refractive error groups. Our results support the previous findings that a deficit of sympathetic facility during nearwork was not a feature of late-onset myopia. However it was found that classifying myopes according to stability of their myopia and their ethnic background was important and this allowed differentiation between accommodation responses and characteristics of the ciliary muscle autonomic inputs, with the greatest difference observed between Caucasian stable myopes and Asian progressing myopes. Progressing myopes, particularly those with an Asian background, demonstrated enhanced susceptibility to nearwork-induced accommodative adaptation and this was suggested to result from a possible parasympathetic dominance and a relative sympathetic deficit to the ciliary muscle. In contrast, stable myopes, particularly those with an Asian background, demonstrated minimal accommodation changes following nearwork (counter-adaptation in some cases), and increased accommodative adaptation with ß-antagonism, suggesting sympathetic dominance as the possible autonomic accommodation control profile. As ethnic background was found to be an important factor, a similar study was also conducted in a group of Hong Kong Chinese children to investigate if enhanced susceptibility to nearwork-induced changes in accommodation may explain in part the high prevalence of myopia in Hong Kong. Despite some minor differences in methodology between the two studies, the Hong Kong stable myopic children demonstrated counter-adaptive changes and greater accommodative adaptation with timolol, findings that were consistent with those of the adult Asian stable myopes. Both Asian progressing myopic children and adults also showed greater accommodative adaptation than the stable myopes and similar response profiles following ß-adrenergic antagonism. Thus a combination of genetically predetermined accommodation profiles that confer high susceptibility and extreme environmental pressures is a likely explanation for the increase in myopia over the past decades in Asian countries. The hypothesis that a sympathetic deficit is linked to myopia was also investigated by comparing the effect of â-stimulation with salbutamol, a ß-agonist, on accommodation with that of ß-antagonism using timolol. It was hypothesized that salbutamol would have the opposite effect of timolol, and that it would have a greater effect on subjects who demonstrated greater accommodative adaptation effects, i.e. the progressing myopes, compared to those who showed minimal changes in accommodation following nearwork. Consistent with the hypothesis, the effect of sympathetic stimulation with salbutamol application was only evident in the progressing myopes whom we hypothesized may have a parasympathetic dominance and a relative sympathetic deficit type of autonomic imbalance while it did not further enhance the rapid accommodative regression profile demonstrated by the stable myopes. Characteristics of the convergence system and the interaction between accommodation and convergence were also investigated in the Hong Kong children. No significant differences in response AC/A ratios between the emmetropic, stable and progressing myopic children were found and it was concluded that elevated AC/A ratios were not associated with higher myopic progression rate in this sample of Hong Kong children. However, ß-adrenergic antagonism with timolol application produced a greater effect on accommodative convergence (AC) in stable myopic children who presumably have a more adequate, robust sympathetic input to the ciliary muscle, but had little effect on AC of progressing myopic children. This finding again points to the possibility that the autonomic control of the accommodation and convergence systems may be different between stable and progressing myopia. The primary contribution of this study to the understanding of myopia development is that differences in the autonomic control of the ciliary muscle may be responsible for producing anomalous accommodation responses. This could have significant impact on retinal image quality and thus results in myopia development. This knowledge may be incorporated into computer models of accommodation and myopia development and provides scope for further investigation of the therapeutic benefits of autonomic agents for myopia control.

People who work in occupations that involve intensive near work are thought to have a higher chance of developing myopia than other people. For example, microscopists in the United Kingdom have a higher prevalence of myopia than that of the general community. The prevalence of myopia in Hong Kong is extremely high (71 %) and Hong Kong Chinese people are particularly susceptible to myopia development and progression due to environmental factors. It is possible that this environmental susceptibility may lead to Hong Kong Chinese microscopists developing even greater levels of myopia. We found that the prevalence of myopia in Hong Kong microscopists (n=47, mean age=31 years) was higher than that of United Kingdom microscopists (87 % c.f. 71 %) and similar aged people within the general Hong Kong population (87 % c.f. 71 %; −4.45 D c.f. -3.00 D). However, while in most microscopists (83 % of 36 microscopists followed for a two-year period) the amount of myopia and vitreous chamber depth increased over a two year monitoring period (−0.11 D, 0.06 mm), the increase was not clinically significant. We hypothesised that the slower myopia progression rate in Hong Kong microscopists may be the result of their older average age (Hong Kong microscopists: 31.7 years c.f. United Kingdom microscopists: 29.7 years). When a person looks into a microscope, excessive accommodation occurs even though the microscope is designed to render the magnified image at optical infinity (zero accommodation and vergence demand). This over accommodation is called instrument myopia. It is possible that this over accommodation is linked to the myopia development and progression that occurs in users of these instruments. We found that instrument myopia remained consistent with different viewing conditions and microscope settings (inexperienced microscopists, n=20, mean age: 24.1 years, mean spherical refractive error: −2.83 D). The magnitude of instrument myopia was not correlated with either the age or refractive error of the microscope user, while it was lower in those users with greater experience (inexperienced microscopists: 1.03 D c.f. experienced microscopists: 0.43 D). As the Hong Kong microscopists (n=10, mean age: 31.2 years, mean spherical refractive error: −3.39 D) who partook in this study were experienced (6.3 years spent working in this field), this may have contributed to the lower myopia progression that was observed. Studies to determine the main contribution to the phenomena of instrument myopia were also conducted. Instrument myopia was not correlated with convergence when looking into microscope (r= −0.224, p=0.342), near phoria (r=0.351, p=0.129), AC/A ratio (r= −0.135, p=0.571), the convergence induced by the excessive accommodative response (r= −0.028, p=0.906), lag of accommodation (r=0.065, p=0.785) and tonic accommodation (r=0.142, p=0.551). We suggest that the main contribution to instrument myopia during microscopy is proximal accommodation due to the awareness of the closeness, caused by the height of the microscope (i.e. the distance between the viewer and the table where the microscope is placed), during microscopy. For example, we found that the magnitude of instrument myopia increased significantly (from 0.64 D to 1.16 D) when the height of the microscope decreased from 50 cm to 35 cm. In conclusion we have added, through direct observation, to the understanding of the characteristics of instrument myopia. Guidelines for new microscopists aimed at minimising the amount of instrument myopia that is experienced have been developed. This information might help to reduce the amount of myopia progression in commencing microscopists.