Octopus Standard Automated Perimetry, Pulsar Perimetry, Moorfields Motion Displacement Test and Heidelberg Retinal Tomography in Glaucoma Detection - A Comparison of Diagnostic Accuracy

Purpose: To investigate the accuracy of 4 clinical instruments in the detection of glaucomatous damage. Methods: 102 eyes of 55 test subjects (Age mean = 66.5yrs, range = [39; 89]) underwent Heidelberg Retinal Tomography (HRTIII), (disc area<2.43); and standard automated perimetry (SAP) using Octopus (Dynamic); Pulsar (TOP); and Moorfields Motion Displacement Test (MDT) (ESTA strategy). Eyes were separated into three groups 1) Healthy (H): IOP<21mmHg and healthy discs (clinical examination), 39 subjects, 78 eyes; 2) Glaucoma suspect (GS): Suspicious discs (clinical examination), 12 subjects, 15 eyes; 3) Glaucoma (G): progressive structural or functional loss, 14 subjects, 20 eyes. Clinical diagnostic precision was examined using the cut-off associated with the p<5% normative limit of MD (Octopus/Pulsar), PTD (MDT) and MRA (HRT) analysis. The sensitivity, specificity and accuracy were calculated for each instrument. Results: See table Conclusions: Despite the advantage of defining glaucoma suspects using clinical optic disc examination, the HRT did not yield significantly higher accuracy than functional measures. HRT, MDT and Octopus SAP yielded higher accuracy than Pulsar perimetry, although results did not reach statistical significance. Further studies are required to investigate the structure-function correlations between these instruments.

Dynamics of two satellites in the 2/1 Mean-Motion resonance: application to the case of Enceladus and Dione

The dynamics of a pair of satellites similar to Enceladus-Dione is investigated with a two-degrees-of-freedom model written in the domain of the planar general three-body problem. Using surfaces of section and spectral analysis methods, we study the phase space of the system in terms of several parameters, including the most recent data. A detailed study of the main possible regimes of motion is presented, and in particular we show that, besides the two separated resonances, the phase space is replete of secondary resonances.

Intraflagellar transport in the developing and mature vertebrate retina

Intraflagellar transport (IFT) is required for the assembly and maintenance of cilia. In this study we analyzed the subcellular localization of IFT proteins in retinal cells by correlative high-resolution immunofluorescence and immunoelectron microscopy. The rod photoreceptor cell was used as a model system to analyze protein distribution in cilia. To date the expression of IFT proteins has been described in the ciliary region without deciphering the precise spatial and temporal subcellular localization of IFT proteins, which was the focus of my work. rnThe establishment of the pre-embedding immunoelectron method was an important first step for the present doctoral thesis. Results of this work reveal the differential localization of IFT20, IFT52, IFT57, IFT88, IFT140 in sub-ciliary compartments and also their presence in non-ciliary compartments of retinal photoreceptor cells. Furthermore, the localization of IFT20, IFT52 and IFT57 in dendritic processes of non-ciliated neurons indicates that IFT protein complexes also operate in non-ciliated cells and may participate in intracellular vesicle trafficking in eukaryotic cells in general.rnIn addition, we have investigated the involvement of IFT proteins in the ciliogenesis of vertebrate photoreceptor cilia. Electron microscopy analyses revealed six morphologically distinct stages. The first stages are characterized by electron dense centriolar satellites and a ciliary vesicle, while the formation of a ciliary shaft and of the light sensitive outer segment disks are features of the later stages. IFT proteins were expressed during all stages of photoreceptor cell development and found to be associated with the ciliary apparatus. In addition to the centriole and basal body IFT proteins are present in the photoreceptor cytoplasm, associated with centriolar satellites, post-Golgi vesicles and with the ciliary vesicle. Therewith the data provide an evidence for the involvement of IFT proteins during ciliogenesis, including the formation of the ciliary vesicle and the elongation of the primary cilium of photoreceptor cells. Moreover, the cytoplasmic localization of IFT proteins in the absence of a ciliary shaft in early stages of ciliogenesis indicates roles of IFT proteins beyond their well-established function for IFT in mature cilia and flagella. rn

Primary ciliary dyskinesia

Primary ciliary dyskinesia (PCD) is an autosomal recessive disease with an incidence estimated between 1:2,000 and 1:40,000. Ciliated epithelia line the airways, nasal and sinus cavities, Eustachian tube and fallopian tubes. Congenital abnormalities of ciliary structure and function impair mucociliary clearance. As a consequence, patients present with chronic sinopulmonary infections, recurrent glue ear and female subfertility. Similarities in the ultrastructure of respiratory cilia, nodal cilia and sperm result in patients with PCD also presenting with male infertility, abnormalities of left-right asymmetry (most commonly situs inversus totalis) and congenital heart disease. Early diagnosis is essential to ensure specialist management of the respiratory and otological complications of PCD. Diagnostic tests focus on analysis of ciliary function and electron microscopy structure. Analysis is technically difficult and labour intensive. It requires expertise for interpretation, restricting diagnosis to specialist centres. Management is currently based on the consensus of experts, and there is a pressing need for randomised clinical trials to inform treatment.

Moving along the mental number line: Interactions between whole-body motion and numerical cognition

Active head turns to the left and right have recently been shown to influence numerical cognition by shifting attention along the mental number line. In the present study, we found that passive whole-body motion influences numerical cognition. In a random-number generation task (Experiment 1), leftward and downward displacement of participants facilitated small number generation, whereas rightward and upward displacement facilitated the generation of large numbers. Influences of leftward and rightward motion were also found for the processing of auditorily presented numbers in a magnitude-judgment task (Experiment 2). Additionally, we investigated the reverse effect of the number-space association (Experiment 3). Participants were displaced leftward or rightward and asked to detect motion direction as fast as possible while small or large numbers were auditorily presented. When motion detection was difficult, leftward motion was detected faster when hearing small number and rightward motion when hearing large number. We provide new evidence that bottom-up vestibular activation is sufficient to interact with the higher-order spatial representation underlying numerical cognition. The results show that action planning or motor activity is not necessary to influence spatial attention. Moreover, our results suggest that self-motion perception and numerical cognition can mutually influence each other.

Management of primary ciliary dyskinesia in European children: recommendations and clinical practice

The European Respiratory Society Task Force on primary ciliary dyskinesia (PCD) in children recently published recommendations for diagnosis and management. This paper compares these recommendations with current clinical practice in Europe. Questionnaires were returned by 194 paediatric respiratory centres caring for PCD patients in 26 countries. In most countries, PCD care was not centralised, with a median (interquartile range) of 4 (2-9) patients treated per centre. Overall, 90% of centres had access to nasal or bronchial mucosal biopsy. Samples were analysed by electron microscopy (77%) and ciliary function tests (57%). Nasal nitric oxide was used for screening in 46% of centres and saccharine tests in 36%. Treatment approaches varied widely, both within and between countries. European region, size of centre and the country's general government expenditure on health partly defined availability of advanced diagnostic tests and choice of treatments. In conclusion, we found substantial heterogeneity in management of PCD within and between countries, and poor concordance with current recommendations. This demonstrates how essential it is to standardise management and decrease inequality between countries. Our results also demonstrate the urgent need for research: to simplify PCD diagnosis, to understand the natural history and to test the effectiveness of interventions.

Being Moved by the Self and Others: Influence of Empathy on Self-Motion Perception

BACKGROUND: The observation of conspecifics influences our bodily perceptions and actions: Contagious yawning, contagious itching, or empathy for pain, are all examples of mechanisms based on resonance between our own body and others. While there is evidence for the involvement of the mirror neuron system in the processing of motor, auditory and tactile information, it has not yet been associated with the perception of self-motion. METHODOLOGY/PRINCIPAL FINDINGS: We investigated whether viewing our own body, the body of another, and an object in motion influences self-motion perception. We found a visual-vestibular congruency effect for self-motion perception when observing self and object motion, and a reduction in this effect when observing someone else's body motion. The congruency effect was correlated with empathy scores, revealing the importance of empathy in mirroring mechanisms. CONCLUSIONS/SIGNIFICANCE: The data show that vestibular perception is modulated by agent-specific mirroring mechanisms. The observation of conspecifics in motion is an essential component of social life, and self-motion perception is crucial for the distinction between the self and the other. Finally, our results hint at the presence of a "vestibular mirror neuron system".

Towards an Earlier Diagnosis of Primary Ciliary Dyskinesia: Which Patients Should Undergo Detailed Diagnostic Testing?

Primary ciliary dyskinesia is a rare heterogeneous recessive genetic disorder of motile cilia, leading to chronic upper and lower respiratory symptoms. Prevalence is estimated at around 1:10,000, but many patients remain undiagnosed, while others receive the label incorrectly. Proper diagnosis is complicated by the fact that the key symptoms such as wet cough, chronic rhinitis and recurrent upper and lower respiratory infection, are common and nonspecific. There is no single gold standard test to diagnose PCD. Presently, the diagnosis is made by augmenting the medical history and physical examination with in patients with a compatible medical history following a demanding combination of tests including nasal nitric oxide, high- speed video microscopy, transmission electron microscopy, genetics, and ciliary culture. These tests are costly and need sophisticated equipment and experienced staff, restricting use to highly specialised centers. Therefore, it would be desirable to have a screening test for identifying those patients who should undergo detailed diagnostic testing. Three recent studies focused on potential screening tools: one paper assessed the validity of nasal nitric oxide for screening, and two studies developed new symptom-based screening tools. These simple tools are welcome, and hopefully remind physicians whom to refer for definitive testing. However, they have been developed in tertiary care settings, where 10 to 50% of tested patients have PCD. Sensitivity and specificity of the tools are reasonable, but positive and negative predictive values may be poor in primary or secondary care settings. While these studies take an important step forward towards an earlier diagnosis of PCD, more remains to be done before we have tools tailored to different health care settings.

Polaris, a Protein Involved in Left-Right Axis Patterning, Localizes to Basal Bodies and Cilia

Mutations in Tg737 cause a wide spectrum of phenotypes, including random left-right axis specification, polycystic kidney disease, liver and pancreatic defects, hydrocephalus, and skeletal patterning abnormalities. To further assess the biological function of Tg737 and its role in the mutant pathology, we identified the cell population expressing Tg737 and determined the subcellular localization of its protein product called Polaris. Tg737 expression is associated with cells possessing either motile or immotile cilia and sperm. Similarly, Polaris concentrated just below the apical membrane in the region of the basal bodies and within the cilia or flagellar axoneme. The data suggest that Polaris functions in a ciliogenic pathway or in cilia maintenance, a role supported by the loss of cilia on the ependymal cell layer in ventricles of Tg737orpk brains and by the lack of node cilia in Tg737Δ2-3βGal mutants.

Kinesin molecular motors: Transport pathways, receptors, and human disease

Kinesin molecular motor proteins are responsible for many of the major microtubule-dependent transport pathways in neuronal and non-neuronal cells. Elucidating the transport pathways mediated by kinesins, the identity of the cargoes moved, and the nature of the proteins that link kinesin motors to cargoes are areas of intense investigation. Kinesin-II recently was found to be required for transport in motile and nonmotile cilia and flagella where it is essential for proper left-right determination in mammalian development, sensory function in ciliated neurons, and opsin transport and viability in photoreceptors. Thus, these pathways and proteins may be prominent contributors to several human diseases including ciliary dyskinesias, situs inversus, and retinitis pigmentosa. Kinesin-I is needed to move many different types of cargoes in neuronal axons. Two candidates for receptor proteins that attach kinesin-I to vesicular cargoes were recently found. One candidate, sunday driver, is proposed to both link kinesin-I to an unknown vesicular cargo and to bind and organize the mitogen-activated protein kinase components of a c-Jun N-terminal kinase signaling module. A second candidate, amyloid precursor protein, is proposed to link kinesin-I to a different, also unknown, class of axonal vesicles. The finding of a possible functional interaction between kinesin-I and amyloid precursor protein may implicate kinesin-I based transport in the development of Alzheimer's disease.

Evidence for reciprocal antagonism between motion sensors tuned to coarse and fine features

Early visual processing analyses fine and coarse image features separately. Here we show that motion signals derived from fine and coarse analyses are combined in rather a surprising way: Coarse and fine motion sensors representing the same direction of motion inhibit one another and an imbalance can reverse the motion perceived. Observers judged the direction of motion of patches of filtered two-dimensional noise, centered on 1 and 3 cycles/deg. When both sets of noise were present and only the 3 cycles/deg noise moved, judgments were reversed at short durations. When both sets of noise moved, judgments were correct but sensitivity was impaired. Reversals and impairments occurred both with isotropic noise and with orientation-filtered noise. The reversals and impairments could be simulated in a model of motion sensing by adding a stage in which the outputs of motion sensors tuned to 1 and 3 cycles/deg and the same direction of motion were subtracted from one another. The subtraction model predicted and we confirmed in experiments with orientation-filtered noise that if the 1 cycle/deg noise flickered and the 3 cycles/deg noise moved, the 1 cycle/deg noise appeared to move in the opposite direction to the 3 cycles/deg noise even at long durations.

Amateurism and the Aesthetics of Lego Stop-Motion on YouTube

Do the “democratization” of media and the proliferation of online participatory culture undermine the aesthetic hegemony of professional filmmakers? This article is a case study of both more and less popular animated Lego videos, also called “brickfilms,” that asks how amateur videos adhere to and/or depart from professionalized aesthetic standards. It addresses the definitions of professionalism and amateurism and proposes that the dichotomy between democratization and ongoing elitism is insufficient to describe the complex dialogue between professional film aesthetics and amateur production—a dialogue that is diverse but nonetheless follows certain patterns. These patterns link Lego videos to silent era cinema as well as contemporary professional live-action and stop-motion animation. Furthermore, a mixture of parody, pastiche, and homage suggest that amateur work has a variety of affective relationships to professional work. Ultimately, amateur filmmaking indicates a negotiation of professional standards rather than slavish adherence.

In vivo analysis of ciliary muscle morphologic changes with accommodation and axial ametropia

Purpose. To use anterior segment optical coherence tomography (AS-OCT) to analyze ciliary muscle morphology and changes with accommodation and axial ametropia. Methods. Fifty prepresbyopic volunteers, aged 19 to 34 years were recruited. High-resolution images were acquired of nasal and temporal ciliary muscles in the relaxed state and at stimulus vergence levels of -4 and -8 D. Objective accommodative responses and axial lengths were also recorded. Two-way, mixed-factor analyses of variance (ANOVAs) were used to assess the changes in ciliary muscle parameters with accommodation and determine whether these changes are dependent on the nasal–temporal aspect or axial length, whereas linear regression analysis was used to analyze the relationship between axial length and ciliary muscle length. Results. The ciliary muscle was longer (r = 0.34, P = 0.02), but not significantly thicker (F = 2.84, P = 0.06), in eyes with greater axial length. With accommodation, the ciliary muscle showed a contractile shortening (F = 42.9. P < 0.001), particularly anteriorly (F = 177.2, P < 0.001), and a thickening of the anterior portion (F= 46.2, P < 0.001). The ciliary muscle was thicker (F = 17.8, P < 0.001) and showed a greater contractile response on the temporal side. Conclusions. The accommodative changes observed support an anterior, as well as centripetal, contractile shift of ciliary muscle mass.