Effects of mitomycin C on glaucoma filtration capsules.

One of the leading causes of implantable device failure is build up of scar tissue on the device. Approaches to address this complication range from choosing device materials that prevent cell adhesion to treatment with potent antifibrotic medications such as mitomycin C. We examined the collagen matrix around aqueous shunt implants in rabbit eyes and found the filtration capsule formed around these devices is not composed of scar tissue. Rather collagen deposition is highly organized with collagen bundles oriented along stress axes. We also examined adjacent tissue deposition in mitomycin C treated animals and found decreased vascularization, condensed collagen in Tenon's capsule with more collagen bundles less well formed than those in the control eye of the same animal. The sclera was thicker under the plate than at the opposite side of the same eye. Structural and functional evaluation correlates with the clinical paradox that patients treated with mitomycin C have lower initial pressures with adjunct drug treatment but lower success rates than the control population after 18 months.

Modeling a parallel L4 neuron array of the fly (Musca domestica) vision system with a sequential processor.

At RMBS 2001 Olson presented a novel approach to image edge detection based on the vision system of the common house fly, Musca domestica [1]. Biologically based vision systems are inherently parallel and the vision related cells form a self-contained cartridge, ommatidium, which is duplicated across the surface of the fly's eye. Histological evidence provides the interconnection both within the vision cartridge and the connections to adjacent cartridges. Due to the parallel nature of biologically inspired vision systems, they outperform computer based digital vision systems in speed performance and memory requirements. Olson provided a model of the cartridge with its intra- and inter-connections. This model, rendered in MATLAB and Excel, demonstrated the feasibility of edge detection in the first several synaptic cellular connections within the cartridge. His results demonstrated how edge detection and object movements are easily obtained using a biologically based vision model. He demonstrated the model using simple rectangular and circular objects. We term this work Olson's Algorithm. We have extended Olson's Algorithm into a high-resolution model using a standard off-the-shelf frame grabber. Although, the frame grabber is a digitally based instrument, its image planes are used to model the photoreceptor layer (R1-R6), the L1, L2 monopolar cell layer, and also the monopolar L4 cell layer. The connections between these cells are programmed in "C". The high-resolution model demonstrates the feasibility of using a biologically based vision system in a real world application. Furthermore, it allows object segmentation, movement, and tracking to be modeled prior to implementation in parallel analog hardware.

Surface tension controls capsule thickness and collagen orientation in glaucoma shunt devices.

Surgical implants to shunt aqueous humor from the eyes of glaucoma patients have been used with limited success, due to a buildup of fibrous tissue in the capsule that causes it to fail as a filtration device. Previous studies suggested that fibers orient along the principal stress lines--surface tension on the capsule directs collagen growth in order to strengthen the stretched membrane. The more tension on the capsule, the thicker the fibrous matrix. In the present study, we analyze collagen fibril and fiber bundle structure to determine whether similar stresses were placed on capsules formed around different implants. We used transmission electron micrographs and light microscopy. Results showed similar structure and collagen fiber bundle densities. This confirmed our previous conclusion that choosing a geometry that reduces surface tension minimizes capsule fibrosis and improves filtration.

Modeling the L4 neuron of the fly (Musca domestica) vision system.

Vision systems based on digital image processing techniques are limited in a variety of areas, particularly speed and memory. Contrast enhancement, image segmentation, object recognition, and object tracking require extensive processing. Biological vision systems drastically outperform computer based digital vision systems in these areas. The animal retina is composed of processing layers with specialized neural cells designed to enhance contrast, segment images, and even produce temporal information. In the vision system of the fly, Musca domestica, the L1, L2, and L4 monopolar cells are of particular interest. The photoreceptor terminals R1 through R6 and L1 and L2 form a cartridge with current shunting inhibition that enhances contrast at the first synaptic contact. L1 and L2 cells are thought to exaggerate contrast while also providing a data reduction encoding scheme to increase communication efficiency with L4 cells and the inner plexiform layer. Research conducted by the authors attempts to simulate the encoding scheme of L1, L2, and L4, and the interactions of these three monopolar cells. This paper proposes that L1 and L2 encode edge information and orientation related to a single cartridge via a sinusoidal modulation scheme. L4 mediates information processing between cartridges via three bi-directional dendritic communication with adjacent L4 cells. Finally, we propose that L4 also synthesizes and forwards the edge orientation information and image movement information to the medulla. A single cartridge simulation was conducted using Matlab. Simulation results will be compared to actual signals taken from the fly eye. Because the fly eye is modular, the goal of this research is to implement the L1, L2, and L4 cell function in analog hardware--the result being a real-time parallel analog vision system.

Predicting language outcomes for young prelinguistic children with developmental delay.

The purpose of this study was to examine potential relationships between children's prelinguistic communication behaviors and subsequent (12 months later) expressive and receptive language outcomes. Participants included 25 toddlers with developmental delay and their mothers. The dyads were observed during natural interactions at 6-month intervals over a 12-month period for a total of 3 observation points (O1, O2, O3). Children's rate of nonverbal behavior that is often perceived as communication by adults was identified at O1 and O2. In the investigation, the children's intentional nonverbal communication acts all included coordinated attention between the communication referent and the adult. The other types of prelinguistic communication behavior, termed gestural indicating behavior and social interaction signals, were produced without coordinated attention to the adult. Receptive and expressive language test scores and spontaneous word productions were analyzed at O3 and served as outcome measures in regression analyses. Results indicated that rate of intentional nonverbal communication at O1 was a predictor of spontaneous word productions at O3. At O2, rate of intentional communication and rate of gestural indicating behavior predicted subsequent language outcomes as measured by the Sequenced Inventory of Communication Development-Revised. The results are consistent with previous findings for intentional nonverbal communication that includes coordinated attention, but additionally demonstrate that prelinguistic behavior lacking coordinated attention also bears a relationship to subsequent language outcome. Discussion of observed patterns focuses on child and adult factors that may motivate the transition from prelinguistic to early symbolic communication.

Performance of a new, low-volume, high-surface area aqueous shunt in normal rabbit eyes.

PURPOSE: This experimental study was conducted to report perfusion characteristics of small diameter, cylindrical aqueous shunts in normal rabbit eyes and to test the hypothesis that decreasing bleb diameter would decrease capsular fibrosis, as evidenced by a thinner capsule forming around the implant. These two properties increase hydraulic conductivity of the fibrous membrane forming around the device, resulting in a more effective filtering shunt. METHODS: Cylindrical latex tubes with the distal portion of the sidewall removed were implanted under the conjunctiva. The proximal, intact end of tubing was inserted into the anterior chamber and ligated to prevent hypotony. The ligature was released after 1 week to inflate the bleb. Animals were again anesthetized at 6 or 12 weeks after ligature release and in vivo perfusion experiments conducted using a miniperfusion system and a water manometer. Perfusion of the implant with latex microspheres was performed before the animals were killed. Capsule diameters were measured in situ using calipers under a dissecting microscope after excision of orbital tissues and before fixation for histologic study. Membrane hydraulic conductivity (outflow per unit membrane area at unitary pressure gradient, microL/min/mm2/mmHg) was calculated using data obtained during perfusion experiments and compared with results of other studies. Capsule thickness was measured histologically. RESULTS: Cylindrical filtration membranes with thin (15-20 microm) capsules formed around latex implants. Bleb diameters consistently measured 1 mm at all points along their length before formaldehyde fixation. Hydraulic conductivity was measured and found to be eight times higher than that reported for capsules around conventional implants. Decreased diameter (16:1 for Baerveldt and 13:1 for Molteno implants) produced a proportional decrease in surface tension on the wall. This resulted in decreased capsule thickness, from 222 microm for Baerveldt implants in rabbit eyes and from 150 microm for Molteno implants in monkey eyes to less than 20 microm for the shunting device studied here. CONCLUSION: As a consequence of Laplace's law, reduction in bleb diameter reduces surface tension on the bleb, reducing capsular fibrosis and consequently capsule thickness, thus increasing hydraulic conductivity. Increased hydraulic conductivity increases the effectiveness of the filtering surface. Cylindrical geometry allows reduced bleb volume yet maintains total surface area that is proportional to the length of the implant, which is unlimited and customizable for each eye by simply cutting the length of implant needed.

Parallel image segmentation using the L4 network.

Each processing element in the outer plexiform layer of the fly's (Musca domestica) compound eye has a single copy of a monopolar cell called L4 whose function is still unknown. This paper proposes that L4 acts as an image segmentor receiving data from the L1 and L2 cell layer above it. The photoreceptor terminals R1 through R6 and L1 and L2 form a cartridge with shunting current inhibition that enhances contrast at the first synaptic contact. The photoreceptors feeding their respective terminals share a common optical axis. What was realized for this entire structure that led up to and included L1 and L2, was that it forms a single processing element which outputs a weighted function based on current shunting between the photoreceptor axon terminals around L1 and L2. Thus the basic biological 'algorithm' that this paper proposes for L1 and L2 involves a summation of the differences between a central reference cell (referred to as Rref) and the six neighboring photoreceptor terminals R1-R6 within the cartridge of L1 and L2. Simulation implementing this simple algorithm on a hexagonal packed matrix in Matlab, suggest that objects with even small differences in intensity with the background, can readily be distinguished from the background. This high pass filter biological model allows edge detection and segmentation, independent of scale in a parallel, modular fashion. Implementation of such a biological algorithm using analog circuitry forms a preprocessing unit that introduces virtually no delay in the processing of image information, in comparison to present DSP techniques, that require iterative approaches and costly computing time.

A retina with parallel input and pulsed output, extracting high-resolution information.

Animal eyes resolve images 10-100 times better than either the acceptance angle of a single photoreceptor or the center-to-center distance between neighboring photoreceptors. A new model of the fly's visual system emulates this improved performance, offering a different approach to subpixel resolution. That an animal without a cortex is capable of this performance suggests that high level computation is not involved. The model takes advantage of a photoreceptor cell's internal structure for capturing and transducing light. This organelle is a waveguide. Neurocircuitry exploits the waveguide's optical nonlinearities, namely the shoulder region of its gaussian, angular-sensitivity profile, to extract high resolution information from the visual scene. The receptive fields of optically disparate inputs overlap in space. Photoreceptor input is continuous rather than discretely sampled. The output of the integrating module is a signal proportional to the position of the target within the detector array. Input imbalance at the level of the photodiode modules is detected by circuitry connecting neighboring visual elements. A pulsed network of these connections forms a parallel array that segments edges of an object and continuously reports its position to the underlying layer of feature extractors, offering a new approach to real time processing with high resolution and reduced computational load.

Pathophysiology of artificial aqueous drainage in primate eyes with molteno implants.

Single-plate Molteno implants were installed in two stages in glaucomatous monkey eyes. This device shunts aqueous from the anterior chamber to periocular orbital tissues. The mechanism of aqueous filtration and absorption was explored using flow studies, fluorescently labeled microspheres and histological examination of tissues. Flow studies indicated that the capsule around the explant functions by a passive mechanism, shunting aqueous into the extracellular space. Outflow is proportional to capsule surface area. Latex microspheres (0.2 mum and smaller) passed freely through the capsule, giving the impression of an open sieve. The presence of microspheres in the episcleral wall of the capsule indicates that all surfaces contribute to filtration. A concentration gradient of particles in the extracapsular space, away from the bleb surface, suggests that the capsule itself limits filtration rate.

Morphologic and physiologic effects of artificial tear formulations on corneal epithelial derived cells.

The biological effects of four commercially available artificial tear formulations were evaluated using sensitive in vitro techniques. Two of the formulations contained ingredients implicated in cell damage; the other two products were not chemically preserved, and their components have not been reported to damage corneal tissue. We assayed the effects of these formulations on viability, morphology, and physiology in corneal cell (SIRC) cultures. Their effect on the hydration of excised rabbit corneas was also determined. In all formulations, cell viability declined with time relative to control cells, but the time course varied significantly. Viability remained at 100% for 6 h in an unpreserved carboxymethylcellulose-based product (CMC-U), and decreased to 50% after greater than 16 hours. Viability decreased to 50% in 3 h for the other unpreserved, polyvinyl alcohol-based product (PVA-U), and in 1 h for a hydroxypropylmethylcellulose formulation (HPMC-P) that contains edetate disodium (EDTA). Cells in a preserved formulation (PVA-P), using polyvinyl alcohol as the polymer and containing EDTA and benzalkonium chloride (BAK), failed to survive even 15 min of treatment. Overall, cells treated with the unpreserved products were nearly indistinguishable from those in the control solution with respect to morphology, electrophysiology, and corneal hydration. Also, the relative ranking from least to most deleterious (control less than CMC-U less than PVA-U less than HPMC-P less than PVA-P) was consistent across several measures. Of the preserved formulations, HPMC-P, which contains the chelating agent EDTA as an additive, was less damaging than was PVA-P, which contains two chemicals, EDTA and BAK, that reportedly damage cells.

Partner sensitivity to communication behavior of young children with developmental disabilities.

Aspects of partner sensitivity to communication behaviors of 24 presymbolic children with developmental disabilities were examined. The children were grouped according to their movement abilities (normal vs. abnormal patterns) and communication status (intentional vs. preintentional). Participating communication partners were those with whom the children interacted on a regular basis and included their mothers, early childhood special educators, and speech-language pathologists. Procedures were developed whereby the partners served as informants in order to provide information regarding (a) recognition of the children's communicative cues and (b) consistency of cue recognition and descriptions across partners. Results indicated wide individual variability in the partners' basic recognition abilities as well as their consistency with each other. Further, the observed variations could not be attributed to the children's movement and communication abilities. It was concluded that sensitivity, as measured in the present investigation, was highly partner-child specific, with some children likely to be exposed to more optimal interactions than others.

Early phonological behavior in normal-speaking and language disordered children: evidence for a synergistic view of linguistic disorders.

Various aspects of the phonological behavior of three normal-speaking and three language disordered children, matched on the basis of mean utterance length, sex, and cognitive development, were compared. The children's spontaneous speech was analyzed to reveal selection constraints inferred from characteristics of the adult form of the words attempted by the child, production constraints inferred from characteristics of the children's productions, phonological processes, and five dimensions of phonological variability. While some individual variation was noted, no substantial group differences were revealed. The phonologies of the normal-speaking and language disordered children were strikingly similar. The implications of these similarities are discussed in terms of a synergistic view of linguistic disorders and remediation.

Children's imitations of lexical items.

3 experiments are reported in which the role of imitation in the acquisition of certain lexical items and factors influencing children's tendency to imitate these lexical items were examined. Imitation did not appear to facilitate the subsequent spontaneous use of lexical items. However, children's tendency to imitate lexical items appeared to be influenced by the novelty of the lexical item and its referent, the informativeness of the referent in the situation, and the lexical orientation of the children. The results are consistent with the interpretation that children's imitations involve the use of a supplied and previously unavailable lexical item under circumstances where lexical usage is highly probable.

Understanding indirect requests: an investigation of children's comprehension of pragmatic meanings.

Two experiments examined four-, five-, and six-year-old children's understanding of indirect requests. The experimental tasks required the children to judge the appropriateness of a listener's response to indirect requests involving an affirmative syntactic construction (Can you shut the door?), requests containing a negative element (Can't you answer the phone?), and requests for the state of affairs mentioned in the predicate to be changed (Must you play the piano?). Even the youngest age group exhibited an understanding of the first two types of indirect requests. However, only the six year olds showed any understanding of requests for a change in the state of affairs mentioned in the predicate. Possible factors responsible for children's difficulty with these requests are discussed.

Experimental acquisition of wh-questions in language-disordered children.

Twenty-four language-disordered children were trained, through modeling with a problem-solving set, to produce a question form involving a wh- word-who, what, or where-in a structure requiring either auxiliary is or auxiliary does. Results indicated the subsequent use of the trained auxiliary across wh- words and, to a lesser extent, the subsequent use of untrained as well as trained wh- words. These results suggest that the training of one multioperation structure may result in the acquisition of two partially independent linguistic operations. Such patterns of acquisition could result in an increase in the efficiency of language training.